Vitamin D is a secosteroid hormone exerting neurosteroid-like properties. Its well-known nuclear hormone receptor, and recently proposed as a mitochondrial transcription factor, vitamin D receptor, acts for its primary functions. The second receptor is an endoplasmic reticulum protein, protein disulfide isomerase A3 (PDIA3), suggested to act as a rapid response. Vitamin D has effects on various systems, particularly through calcium metabolism. Among them, the nervous system has an important place in the context of our subject. Recent studies have shown that vitamin D and its receptors have numerous effects on the nervous system. Neurodegeneration is a long-term process. Throughout a human life span, so is vitamin D deficiency. Our previous studies and others have suggested that the out-come of long-term vitamin D deficiency (hypovitaminosis D or inefficient utilization of vitamin D), may lead neurons to be vulnerable to aging and neurodegeneration. We suggest that keeping vitamin D levels at adequate levels at all stages of life, considering new approaches such as agonists that can activate vitamin D receptors, and utilizing other derivatives produced in the synthesis process with UVB are crucial when considering vitamin D-based intervention studies. Given most aspects of vitamin D, this review outlines how vitamin D and its receptors work and are involved in neurodegeneration, emphasizing Alzheimer’s disease.
ChristakosS, DhawanP, VerstuyfA, VerlindenL, CarmelietG (2016) Vitamin D: Metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev96, 365–408.
2.
CekicM, SayeedI, SteinDG (2009) Combination treatment with progesterone and vitamin d hormone may be more effective than monotherapy for nervous system injury and disease. Front Neuroendocrin30, 158–172.
3.
GarcionE, Wion-BarbotN, Montero-MeneiCN, BergerF, WionD (2002) New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab13, 100–105.
4.
HolickM (1995) Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications. Bone17, 107–111.
5.
DursunE, AlayliogluM, BilgicB, HanagasiH, LohmannE, AtasoyIL, CandasE, ArazOS, OnalB, GurvitH, YilmazerS, Gezen-AkD (2016) Vitamin D deficiency might pose a greater risk for ApoEvarepsilon4 non-carrier Alzheimer’s disease patients. Neurol Sci37, 1633–1643.
6.
Gezen-AkD, AlayliogluM, GencG, GunduzA, CandasE, BilgicB, AtasoyIL, ApaydinH, KiziltanG, GurvitH, HanagasiH, ErtanS, YilmazerS, DursunE (2017) GC and VDR SNPs and Vitamin D levels in Parkinson’s disease: The relevance to clinical features. Neuromolecular Med19, 24–40.
7.
Gezen-AkD, AtasoyIL, CandasE, AlayliogluM, YilmazerS, DursunE (2017) Vitamin D receptor regulates amyloid beta 1-42 production with protein disulfide isomerase A3. ACS Chem Neurosci8, 2335–2346.
8.
Gezen-AkD, YilmazerS, DursunE (2014) Why vitamin D in Alzheimer’s disease? The hypothesis. J Alzheimers Dis40, 257–269.
9.
AnnweilerC, DursunE, FeronF, Gezen-AkD, KalueffAV, LittlejohnsT, LlewellynD, MilletP, ScottT, TuckerKL, YilmazerS, BeauchetO (2016) Vitamin D and cognition in older adults: International consensus guidelines. Geriatr Psychol Neuropsychiatr Vieil14, 265–273.
10.
AnnweilerC, DursunE, FeronF, Gezen-AkD, KalueffAV, LittlejohnsT, LlewellynDJ, MilletP, ScottT, TuckerKL, YilmazerS, BeauchetO (2015) ‘Vitamin D and cognition in older adults’: Updated international recommendations. J Intern Med277, 45–57.
11.
DursunE, Gezen-AkD (2019) Vitamin D basis of Alzheimer’s disease: From genetics to biomarkers. Hormones (Athens)18, 7–15.
12.
Gezen-AkD, DursunE (2019) Molecular basis of vitamin D action in neurodegeneration: The story of a team perspective. Hormones (Athens)18, 17–21.
13.
Gezen-AkD, YurttasZ, CamogluT, DursunE (2022) Could amyloid-beta 1-42 or alpha-synuclein interact directly with mitochondrial DNA? A hypothesis. ACS Chem Neurosci13, 2803–2812.
14.
F'eronF, BurneTHJ, BrownJ, SmithE, McGrathJJ, Mackay-SimaA, EylesDW (2005) Developmental vitamin D3 deficiency alters the adult rat brain. Brain Res Bull65, 141–148.
15.
RushL, McCartneyG, WalshD, MackayD (2013) Vitamin D and subsequent all-age and premature mortality: A systematic review. BMC Public Health13, 679.
16.
BikleDD (2011) Vitamin D: An ancient hormone. Exp Dermatol20, 7–13.
17.
IssaL, LeongGM, EismanJA (1997) Molecular mechanism of vitamin D receptor action. Inflamm Res47, 451–475.
18.
FreedmanLP, ArceV, Perez FernandezR (1994) DNA sequences that act as high affinity targets for the vitamin D3 receptor in the absence of the retinoid X receptor. Mol Endocrinol8, 265–273.
19.
KoshyKT (1982) Vitamin D: An update. J Pharm Sci71, 137–153.
20.
HoughtonLA, ViethR (2006) The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr84, 694–697.
21.
SugimotoH, ShiroY (2012) Diversity and substrate specificity in the structures of steroidogenic cytochrome P450 enzymes. Biol Pharm Bull35, 818–823.
22.
ZhuJ, DeLucaHF (2012) Vitamin D 25-hydroxylase - Four decades of searching, are we there yet?Arch Biochem Biophys523, 30–36.
DhawanP, ChristakosS (2010) Novel regulation of 25-hydroxyvitamin D3 24-hydroxylase (24(OH)ase) transcription by glucocorticoids: Cooperative effects of the glucocorticoid receptor, C/EBPb, and the vitamin D receptor in 24(OH)ase transcription. J Cell Biochem110, 1314–1323.
30.
Gezen-AkD, DursunE, YilmazerS (2013) Vitamin D inquiry in hippocampal neurons: Consequences of vitamin D-VDR pathway disruption on calcium channel and the vitamin D requirement. Neurol Sci34, 1453–1458.
31.
SakakiT, SawadaN, KomaiK, ShiozawaS, YamadaS, YamamotoK, OhyamaY, InouyeK (2000) Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24. Eur J Biochem267, 6158–6165.
32.
JonesG, ProsserDE, KaufmannM (2012) 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): Its important role in the degradation of vitamin D. Arch Biochem Biophys523, 9–18.
33.
SlominskiAT, KimTK, SlominskiRM, SongY, JanjetovicZ, PodgorskaE, ReddySB, SongY, RamanC, TangEKY, FabisiakA, BrzeminskiP, SicinskiRR, AtigaddaV, JettenAM, HolickMF, TuckeyRC (2022) Metabolic activation of tachysterol(3) to biologically active hydroxyderivatives that act on VDR, AhR, LXRs, and PPARgamma receptors. FASEB J36, e22451.
34.
SlominskiAT, LiW, KimTK, SemakI, WangJ, ZjawionyJK, TuckeyRC (2015) Novel activities of CYP11A1 and their potential physiological significance. J Steroid Biochem Mol Biol151, 25–37.
35.
SlominskiAT, JanjetovicZ, FullerBE, ZmijewskiMA, TuckeyRC, NguyenMN, SweatmanT, LiW, ZjawionyJ, MillerD, ChenTC, LozanskiG, HolickMF (2010) Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity. PLoS One5, e9907.
36.
HolickMF (2014) Cancer, sunlight and vitamin D. J Clin Transl Endocrinol1, 179–186.
37.
WackerM, HolickMF (2013) Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol5, 51–108.
38.
BaggerlyCA, CuomoRE, FrenchCB, GarlandCF, GorhamED, GrantWB, HeaneyRP, HolickMF, HollisBW, McDonnellSL, PittawayM, SeatonP, WagnerCL, WunschA (2015) Sunlight and vitamin D: Necessary for public health. J Am Coll Nutr34, 359–365.
39.
WaterhamHR, KosterJ, RomeijnGJ, HennekamRC, VrekenP, AnderssonHC, FitzPatrickDR, KelleyRI, WandersRJ (2001) Mutations in the 3beta-hydroxysterol Delta24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis. Am J Hum Genet69, 685–694.
40.
YavuzU, AlayliogluM, SengulB, KarrasSN, Gezen-AkD, DursunE (2021) Protein disulfide isomerase A3 might be involved in the regulation of 24-dehydrocholesterol reductase via vitamin D equilibrium in primary cortical neurons. In Vitro Cell Dev Biol Anim57, 704–714.
41.
LutjohannD (2006) Cholesterol metabolism in the brain: Imortance of 24S-hydroxylation. Acta Neurol Scand Suppl185, 33–42
42.
HermanGE (2003) Disorders of cholesterol biosynthesis: Prototypic metabolic malformation syndromes. Hum Mol Genet12(Spec No 1), R75–R88.
43.
PrabhuAV, LuuW, SharpeLJ, BrownAJ (2016) Cholesterol-mediated degradation of 7-dehydrocholesterol reductase switches the balance from cholesterol to vitamin D synthesis. J Biol Chem291, 8363–8373.
44.
CarlbergC (2014) Genome-wide (over)view on the actions of vitamin D. Front Physiol5, 167.
KalarasMD, BeelmanRB, HolickMF, EliasRJ (2012) Generation of potentially bioactive ergosterol-derived products following pulsed ultraviolet light exposure of mushrooms (Agaricus bisporus). Food Chem135, 396–401.
47.
PasanenAL, Yli-PietilaK, PasanenP, KalliokoskiP, TarhanenJ (1999) Ergosterol content in various fungal species and biocontaminated building materials. Appl Environ Microbiol65, 138–142.
48.
HolickMF, ChenTC, LuZ, SauterE (2007) Vitamin D and skin physiology: A D-lightful story. J Bone Miner Res22(Suppl 2), V28–33.
49.
HolickMF, TianXQ, AllenM (1995) Evolutionary importance for the membrane enhancement of the production of vitamin D3 in the skin of poikilothermic animals. Proc Natl Acad Sci U S A92, 3124–3126.
DursunE, Gezen-AkD, YilmazerS (2013) A new mechanism for amyloid-beta induction of iNOS: Vitamin D-VDR pathway disruption. J Alzheimers Dis36, 459–474.
55.
Gezen-AkD, DursunE, YilmazerS (2011) The effects of vitamin D receptor silencing on the expression of LVSCC-A1C and LVSCC-A1D and the release of NGF in cortical neurons. PLoS One6, e17553.
56.
DursunE, Gezen-AkD, YilmazerS (2011) A novel perspective for Alzheimer’s disease: Vitamin D receptor suppression by amyloid-beta and preventing the amyloid-beta induced alterations by vitamin D in cortical neurons. J Alzheimers Dis23, 207–219.
57.
EylesDW, BurneTH, McGrathJJ (2013) Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol34, 47–64.
FantiniC, CorinaldesiC, LenziA, MigliaccioS, CrescioliC (2023) Vitamin D as a shield against aging. Int J Mol Sci24, 4546.
60.
CuiX, PelekanosM, LiuPY, BurneTH, McGrathJJ, EylesDW (2013) The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain. Neuroscience236, 77–87.
61.
KesbyJP, CuiX, BurneTH, EylesDW (2013) Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia. Front Cell Neurosci7, 111.
62.
AnnweilerC, SchottAM, AllaliG, BridenbaughSA, KressigRW, AllainP, HerrmannFR, BeauchetO (2010) Association of vitamin D deficiency with cognitive impairment in older women: Cross-sectional study. Neurology74, 27–32.
63.
AnnweilerC, RollandY, SchottAM, BlainH, VellasB, BeauchetO (2012) Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: A 7-year longitudinal study. Dement Geriatr Cogn Disord32, 273–278.
64.
AnnweilerC, FantinoB, SchottAM, Krolak-SalmonP, AllaliG, BeauchetO (2012) Vitamin D insufficiency and mild cognitive impairment: Cross-sectional association. Eur J Neurol19, 1023–1029.
65.
CherniackEP, FlorezH, RoosBA, TroenBR, LevisS (2008) Hypovitaminosis D in the elderly: From bone to brain. J Nutr Health Aging12, 366–373.
66.
EvattML, DeLongMR, KhazaiN, RosenA, TricheS, TangprichaV (2008) Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol65, 1348–1352.
67.
LlewellynDJ, LangaKM, LangIA (2009) Serum 25-hydroxyvitamin D concentration and cognitive impairment. J Geriatr Psychiatry Neurol22, 188–195.
68.
LlewellynDJ, LangIA, LangaKM, Muniz-TerreraG, PhillipsCL, CherubiniA, FerrucciL, MelzerD (2010) Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med170, 1135–1141.
69.
OudshoornC, Mattace-RasoFUS, van der VeldeN, ColinEM, van der CammenTJM (2008) Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with alzheimer’s disease. Dement Geriatr Cogn Disord25, 539–543.
70.
WilkinsCH, ShelineYI, RoeCM, BirgeSJ, MorrisJC (2006) Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry14, 1032–1040.
71.
RoccaWA, HofmannA, BrayneC, BretelerMM, ClarkeM, CopelandJR, DartiguesJF, EngedalK, HagnellO, HeerenTJ (1991) Frequency and distribution of Alzheimer’s Disease in Europe: A collaborative study of 1980-1990 prevalence findings. The EURODEM-Prevalance Research Group. Ann Neurol30, 381–390.
72.
HardyJ (1997) Amyloid, the presenilins and Alzheimer’s disease. Trends Neurosci20, 154–159.
73.
AlayliogluM, Gezen-AkD, DursunE, BilgicB, HanagasiH, ErtanT, GurvitH, EmreM, EkerE, UysalO, YilmazerS (2016) The association between clusterin and APOE polymorphisms and late-onset Alzheimer disease in a Turkish cohort. J Geriatr Psychiatry Neurol29, 221–226.
74.
AtasoyIL, DursunE, Gezen-AkD, Metin-ArmaganD, OzturkM, YilmazerS (2017) Both secreted and the cellular levels of BDNF attenuated due to tau hyperphosphorylation in primary cultures of cortical neurons. J Chem Neuroanat80, 19–26.
75.
Gezen-AkD, AtasoyIL, CandasE, AlayliogluM, DursunE (2018) The transcriptional regulatory properties of amyloid beta 1-42 may include regulation of genes related to neurodegeneration. Neuromolecular Med20, 363–375.
76.
DursunE, Gezen-AkD, YilmazerS (2013) Beta amyloid suppresses the expression of the vitamin d receptor gene and induces the expression of the vitamin d catabolic enzyme gene in hippocampal neurons. Dement Geriatr Cogn Disord36, 76–86.
77.
YuJ, Gattoni-CelliM, ZhuH, BhatNR, SambamurtiK, Gattoni-CelliS, KindyMS (2011) Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AbetaPP transgenic mice. J Alzheimers Dis25, 295–307.
78.
ThotaC, FarmerT, GarfieldRE, MenonR, Al-HendyA (2013) Vitamin D elicits anti-inflammatory response, inhibits contractile-associated proteins, and modulates toll-like receptors in human myometrial cells. Reprod Sci20, 463–475.
Fernandes de AbreuDA, EylesD, FeronF (2009) Vitamin D, a neuro-immunomodulator: Implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology34(Suppl 1), S265–S277.
81.
LandelV, AnnweilerC, MilletP, MorelloM, FeronF (2016) Vitamin D, cognition and Alzheimer’s disease: The therapeutic benefit is in the D-tails. J Alzheimers Dis53, 419–444.
82.
LandelV, MilletP, BarangerK, LoriodB, FeronF (2016) Vitamin D interacts with Esr1 and Igf1 to regulate molecular pathways relevant to Alzheimer’s disease. Mol Neurodegener11, 22.
83.
MizwickiMT, MenegazD, ZhangJ, Barrientos-DuránA, TseS, CashmanJR, GriffinPR, FialaM (2011) Genomic and nongenomic signaling induced by 1α,25(OH)2-Vitamin D3 promotes the recovery of amyloid-β phagocytosis by Alzheimer’s disease macrophages. J Alzheimers Dis29, 51–62.
84.
MizwickiMT, LiuG, FialaM, MagpantayL, SayreJ, SianiA, MahanianM, WeitzmanR, HaydenEY, RosenthalMJ, NemereI, RingmanJ, TeplowDB (2013) 1alpha,25-dihydroxyvitamin D3 and resolvin D1 retune the balance between amyloid-beta phagocytosis and inflammation in Alzheimer’s disease patients. J Alzheimers Dis34, 155–170.
85.
BrionesTL, DarwishH (2012) Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden. J Neuroinflammation9, 244.
86.
DursunE, Gezen-AkD, YilmazerS (2014) The influence of vitamin D treatment on the inducible nitric oxide synthase (INOS) expression in primary hippocampal neurons. Noro Psikiyatr Ars51, 163–168.
87.
Gezen-AkD, DursunE, YilmazerS (2014) The effect of vitamin D treatement on nerve growth factor release (NGF) in hippocampal neurons. Noro Psikiyatr Ars51, 157–162.
88.
MasoumiA, GoldensonB, GhirmaiS, AvagyanH, ZaghiJ, AbelK, ZhengX, Espinosa-JeffreyA, MahanianM, LiuPT, HewisonM, MizwickieM, CashmanJ, FialaM (2009) 1alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer’s disease patients. J Alzheimers Dis17, 703–717.
89.
FialaM, MizwickiMT (2011) Neuroprotective and immune effects of active forms of vitamin D3 and docosahexaenoic acid in Alzheimer disease patients. Funct Foods Health Dis12, 545–554.
90.
ItoS, OhtsukiS, NezuY, KoitabashiY, MurataS, TerasakiT (2011) 1alpha,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-beta peptide(1-40) from mouse brain across the blood-brain barrier. Fluids Barriers CNS8, 20.
91.
MariniF, BartocciniE, CascianelliG, VoccoliV, BavigliaMG, MagniMV, Garcia-GilM, AlbiE (2010) Effect of 1alpha,25-dihydroxyvitamin D3 in embryonic hippocampal cells. Hippocampus20, 696–705.
92.
SonnenbergJ, LuineVN, KreyLC, ChristakosS (1986) 1,25-Dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei. Endocrinology118, 1433–1439.
93.
KumarPT, AntonyS, NandhuMS, SadanandanJ, NaijilG, PauloseCS (2011) Vitamin D3 restores altered cholinergic and insulin receptor expression in the cerebral cortex and muscarinic M3 receptor expression in pancreatic islets of streptozotocin induced diabetic rats. J Nutr Biochem22, 418–425.
94.
PeeyushKT, SavithaB, SherinA, AnjuTR, JesP, PauloseCS (2010) Cholinergic, dopaminergic and insulin receptors gene expression in the cerebellum of streptozotocin-induced diabetic rats: Functional regulation with vitamin D3 supplementation. Pharmacol Biochem Behav95, 216–222.
95.
Peeyush KumarT, PaulJ, AntonyS, PauloseCS (2011) Expression of cholinergic, insulin, vitamin D receptors and GLUT 3 in the brainstem of streptozotocin induced diabetic rats: Effect of treatment with vitamin D(3). Neurochem Res36, 2116–2126.
96.
SmithMP, Fletcher-TurnerA, YurekDM, CassWA (2006) Calcitriol protection against dopamine loss induced by intracerebroventricular administration of 6-hydroxydopamine. Neurochem Res31, 533–539.
97.
CassWA, PetersLE, FletcherAM, YurekDM (2012) Evoked dopamine overflow is augmented in the striatum of calcitriol treated rats. Neurochem Int60, 186–191.
98.
MoonM, SongH, HongHJ, NamDW, ChaMY, OhMS, YuJ, RyuH, Mook-JungI (2013) Vitamin D-binding protein interacts with Abeta and suppresses Abeta-mediated pathology. Cell Death Differ20, 630–638.
99.
NissouMF, BrocardJ, El AtifiM, GuttinA, AndrieuxA, BergerF, IssartelJP, WionD (2013) The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin d3 includes genes limiting the progression of neurodegenerative diseases. J Alzheimers Dis35, 553–564.
100.
GrimmMOW, LauerAA, GrosgenS, ThielA, LehmannJ, WinklerJ, JanitschkeD, HerrC, BeisswengerC, BalsR, GrimmHS, HartmannT (2019) Profiling of Alzheimer’s disease related genes in mild to moderate vitamin D hypovitaminosis. J Nutr Biochem67, 123–137.
101.
SemposCT, VesperHW, PhinneyKW, ThienpontLM, CoatesPM, VitaminDSP (2012) Vitamin D status as an international issue: National surveys and the problem of standardization. Scand J Clin Lab Invest Suppl243, 32–40.
SchleicherRL, SternbergMR, LookerAC, YetleyEA, LacherDA, SemposCT, TaylorCL, Durazo-ArvizuRA, MawKL, Chaudhary-WebbM, JohnsonCL, PfeifferCM (2016) National estimates of serum total 25-hydroxyvitamin D and metabolite concentrations measured by liquid chromatography-tandem mass spectrometry in the US population during 2007-2010. J Nutr146, 1051–1061.
104.
SarafinK, Durazo-ArvizuR, TianL, PhinneyKW, TaiS, CamaraJE, MerkelJ, GreenE, SemposCT, BrooksSP (2015) Standardizing 25-hydroxyvitamin D values from the Canadian Health Measures Survey. Am J Clin Nutr102, 1044–1050.
105.
RabenbergM, Scheidt-NaveC, BuschMA, ThammM, RieckmannN, Durazo-ArvizuRA, DowlingKG, SkrabakovaZ, CashmanKD, SemposCT, MensinkGBM (2018) Implications of standardization of serum 25-hydroxyvitamin D data for the evaluation of vitamin D status in Germany, including a temporal analysis. BMC Public Health18, 845.
106.
McCannJ, AmesBN (2008) Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction?FASEB J22, 982–1001.
107.
LittlejohnsTJ, HenleyWE, LangIA, AnnweilerC, BeauchetO, ChavesPH, FriedL, KestenbaumBR, KullerLH, LangaKM, LopezOL, KosK, SoniM, LlewellynDJ (2014) Vitamin D and the risk of dementia and Alzheimer disease. Neurology83, 920–928.
108.
GengT, LuQ, WanZ, GuoJ, LiuL, PanA, LiuG (2022) Association of serum 25-hydroxyvitamin D concentrations with risk of dementia among individuals with type 2 diabetes: A cohort study in the UK Biobank. PLoS Med19, e1003906.
109.
Le FlochM, GautierJ, AnnweilerC (2022) Vitamin D concentration and motoric cognitive risk in older adults: Results from the Gait and Alzheimer Interactions Tracking (GAIT) Cohort. Int J Environ Res Public Health19, 13086.
110.
LicherS, de BruijnR, WoltersFJ, ZillikensMC, IkramMA, IkramMK (2017) Vitamin D and the risk of dementia: The Rotterdam Study. J Alzheimers Dis60, 989–997.
111.
BuellJS, Dawson-HughesB, ScottTM, WeinerDE, DallalGE, QuiWQ, BergethonP, RosenbergIH, FolsteinMF, PatzS, BhadeliaRA, TuckerKL (2010) 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology74, 18–26.
112.
AnnweilerC, Montero-OdassoM, LlewellynDJ, Richard-DevantoyS, DuqueG, BeauchetO (2013) Meta-Analysis of memory and executive dysfunctions in relation to vitamin D. J Alzheimers Dis37, 147–171.
113.
AnnweilerC, LlewellynDJ, BeauchetO (2013) Low serum vitamin D concentrations in Alzheimer’s disease: A systematic review and meta-analysis. J Alzheimers Dis33, 659–674.
114.
ChaiB, GaoF, WuR, DongT, GuC, LinQ, ZhangY (2019) Vitamin D deficiency as a risk factor for dementia and Alzheimer’s disease: An updated meta-analysis. BMC Neurol19, 284.
115.
YangK, ChenJ, LiX, ZhouY (2019) Vitamin D concentration and risk of Alzheimer disease: A meta-analysis of prospective cohort studies. Medicine (Baltimore)98, e16804.
116.
JayediA, Rashidy-PourA, Shab-BidarS (2019) Vitamin D status and risk of dementia and Alzheimer’s disease: A meta-analysis of dose-response (dagger). Nutr Neurosci22, 750–759.
117.
AfzalS, BojesenSE, NordestgaardBG (2014) Reduced 25-hydroxyvitamin D and risk of Alzheimer’s disease and vascular dementia. Alzheimers Dement10, 296–302.
118.
GhahremaniM, SmithEE, ChenHY, CreeseB, GoodarziZ, IsmailZ (2023) Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimers Dement (Amst)15, e12404.
119.
KidermanD, Ben-ShabatN, TsurAM, AnisS, WatadA, CohenAD, PazZ, AmitalH (2023) Vitamin D insufficiency is associated with higher incidence of dementia, a large community-based retrospective cohort study. J Geriatr Psychiatry Neurol. doi: 10.1177/08919887231163292.
120.
GrantWB, Al AnoutiF, BoucherBJ, DursunE, Gezen-AkD, JudeEB, KaronovaT, PludowskiP (2022) A narrative review of the evidence for variations in serum 25-hydroxyvitamin D concentration thresholds for optimal health. Nutrients14, 639.
121.
HeaneyRP, DaviesKM, ChenTC, HolickMF, Barger-LuxMJ (2003) Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr77, 204–210.
122.
RossAC, MansonJE, AbramsSA, AloiaJF, BrannonPM, ClintonSK, Durazo-ArvizuRA, GallagherJC, GalloRL, JonesG, KovacsCS, MayneST, RosenCJ, ShapsesSA (2011) The 2011 Dietary Reference Intakes for Calcium and Vitamin D: What dietetics practitioners need to know. J Am Diet Assoc111, 524–527.
123.
BrownLL, CohenB, TaborD, ZappalaG, MaruvadaP, CoatesPM (2018) The vitamin D paradox in Black Americans: A systems-based approach to investigating clinical practice, research, and public health - expert panel meeting report. BMC Proc12, 6.
124.
HolickMF (2007) Vitamin D deficiency. N Engl J Med357, 266–281.
125.
NormanAW, BouillonR (2010) Vitamin D nutritional policy needs a vision for the future. Exp Biol Med (Maywood)235, 1034–1045.
126.
ChalcraftJR, CardinalLM, WechslerPJ, HollisBW, GerowKG, AlexanderBM, KeithJF, Larson-MeyerDE (2020) Vitamin D synthesis following a single bout of sun exposure in older and younger men and women. Nutrients12, 2237.
127.
VranicL, MikolasevicI, MilicS (2019) Vitamin D deficiency: Consequence or cause of obesity?Medicina (Kaunas)55, 541.
128.
GrantWB (2014) Trends in diet and Alzheimer’s disease during the nutrition transition in Japan and developing countries. J Alzheimers Dis38, 611–620.
129.
DezonneRS, PereiraCM, de Moraes MartinsCJ, de AbreuVG, FrancischettiEA (2023) Adiponectin, the adiponectin paradox, and Alzheimer’s Disease: Is this association biologically plausible?Metab Brain Dis38, 109–121.
130.
Flores-CorderoJA, Perez-PerezA, Jimenez-CorteganaC, AlbaG, Flores-BarraganA, Sanchez-MargaletV (2022) Obesity as a risk factor for dementia and Alzheimer’s disease: The role of leptin. Int J Mol Sci23, 5202.
131.
LetraL, SantanaI (2017) The influence of adipose tissue on brain development, cognition, and risk of neurodegenerative disorders. Adv Neurobiol19, 151–161.
132.
LetraL, SantanaI, SeicaR (2014) Obesity as a risk factor for Alzheimer’s disease: The role of adipocytokines. Metab Brain Dis29, 563–568.
133.
Mendiola-PrecomaJ, BerumenLC, PadillaK, Garcia-AlcocerG (2016) Therapies for prevention and treatment of Alzheimer’s disease. Biomed Res Int2016, 2589276.
134.
SanbornV, PreisSR, AngA, DevineS, MezJ, DeCarliC, AuR, AloscoML, GunstadJ (2020) Association between leptin, cognition, and structural brain measures among “early” middle-aged adults: Results from the Framingham Heart Study Third Generation Cohort. J Alzheimers Dis77, 1279–1289.
135.
GharekhaniA, NajafipourF, BaradaranH, TagharrobiP, RezaeeH (2020) The effect of treating vitamin D deficiency or insufficiency on serum adiponectin, leptin and insulin resistance of type 2 diabetes mellitus patients: A pilot study. Iran J Pharm Res19, 86–94.
136.
AnwarMJ, AleneziSK, AlhowailAH (2023) Molecular insights into the pathogenic impact of vitamin D deficiency in neurological disorders. Biomed Pharmacother162, 114718.
137.
Lefevre-ArbogastS, DhanaK, AggarwalNT, ZhangS, AgarwalP, LiuX, LaranjoN, CareyV, SacksF, BarnesLL, ArfanakisK (2021) Vitamin D intake and brain cortical thickness in community-dwelling overweight older adults: A cross-sectional study. J Nutr151, 2760–2767.
138.
BouillonR (2017) Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol13, 466–479.
139.
HolickMF, BinkleyNC, Bischoff-FerrariHA, GordonCM, HanleyDA, HeaneyRP, MuradMH, WeaverCM, Endocrine Society (2011) Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab96, 1911–1930.
140.
HeaneyRP, HolickMF (2011) Why the IOM recommendations for vitamin D are deficient. J Bone Miner Res26, 455–457.
141.
PilzS, MarzW, CashmanKD, KielyME, WhitingSJ, HolickMF, GrantWB, PludowskiP, HiligsmannM, TrummerC, SchwetzV, LerchbaumE, PandisM, TomaschitzA, GrublerMR, GakschM, VerheyenN, HollisBW, RejnmarkL, KarrasSN, HahnA, Bischoff-FerrariHA, ReichrathJ, JordeR, ElmadfaI, ViethR, ScraggR, CalvoMS, van SchoorNM, BouillonR, LipsP, ItkonenST, MartineauAR, Lamberg-AllardtC, ZittermannA (2018) Rationale and plan for vitamin D food fortification: A review and guidance paper. Front Endocrinol (Lausanne)9, 373.
142.
GonenMS, AlayliogluM, DurcanE, OzdemirY, SahinS, KonukogluD, NohutOK, UrkmezS, KucukeceB, BalkanII, KaraHV, BorekciS, OzkayaH, KutlubayZ, DikmenY, KeskindemirciY, KarrasSN, AnnweilerC, Gezen-AkD, DursunE (2021) Rapid and effective vitamin D supplementation may present better clinical outcomes in COVID-19 (SARS-CoV-2) patients by altering serum INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. Nutrients13, 4047.
143.
PilzS, ZittermannA, TrummerC, Theiler-SchwetzV, LerchbaumE, KeppelMH, GrublerMR, MarzW, PandisM (2019) Vitamin D testing and treatment: A narrative review of current evidence. Endocr Connect8, R27–R43.
144.
ThielA, HermannsC, LauerAA, ReichrathJ, ErhardtT, HartmannT, GrimmMOW, GrimmHS (2023) Vitamin D and its analogues: From differences in molecular mechanisms to potential benefits of adapted use in the treatment of Alzheimer’s disease. Nutrients15, 1684.
145.
PlantoneD, PardiniM, CanevaS, De StefanoN (2023) Is there a role of vitamin D in Alzheimer’s disease?CNS Neurol Disord Drug Targets. doi: 10.2174/1871527322666230526164421.
146.
Bischoff-FerrariHA, VellasB, RizzoliR, KressigRW, da SilvaJAP, BlauthM, FelsonDT, McCloskeyEV, WatzlB, HofbauerLC, FelsenbergD, WillettWC, Dawson-HughesB, MansonJE, SiebertU, TheilerR, StaehelinHB, de Godoi Rezende Costa MolinoC, Chocano-BedoyaPO, AbderhaldenLA, EgliA, KanisJA, OravEJ, Group D-HR (2020) Effect of vitamin D supplementation, omega-3 fatty acid supplementation, or a strength-training exercise program on clinical outcomes in older adults: The DO-HEALTH Randomized Clinical Trial. JAMA324, 1855–1868.
147.
MoranC, Scotto di PalumboA, BramhamJ, MoranA, RooneyB, De VitoG, EganB (2018) Effects of a six-month multi-ingredient nutrition supplement intervention of omega-3 polyunsaturated fatty acids, vitamin D, resveratrol, and whey protein on cognitive function in older adults: A randomised, double-blind, controlled trial. J Prev Alzheimers Dis5, 175–183.
148.
PrzybelskiR, AgrawalS, KruegerD, EngelkeJA, WalbrunF, BinkleyN (2008) Rapid correction of low vitamin D status in nursing home residents. Osteoporos Int19, 1621–1628.
149.
SteinMS, SchererSC, LaddKS, HarrisonLC (2011) A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer’s disease. J Alzheimers Dis26, 477–484.
150.
JordeR, KubiakJ, SvartbergJ, FuskevagOM, FigenschauY, MartinaityteI, GrimnesG (2019) Vitamin D supplementation has no effect on cognitive performance after four months in mid-aged and older subjects. J Neurol Sci396, 165–171.
151.
YangT, WangH, XiongY, ChenC, DuanK, JiaJ, MaF (2020) Vitamin D supplementation improves cognitive function through reducing oxidative stress regulated by telomere length in older adults with mild cognitive impairment: A 12-month randomized controlled trial. J Alzheimers Dis78, 1509–1518.
152.
JiaJ, HuJ, HuoX, MiaoR, ZhangY, MaF (2019) Effects of vitamin D supplementation on cognitive function and blood Abeta-related biomarkers in older adults with Alzheimer’s disease: A randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry90, 1347–1352.
153.
AnnweilerC, HerrmannFR, FantinoB, BruggB, BeauchetO (2012) Effectiveness of the combination of memantine plus vitamin D on cognition in patients with Alzheimer disease: A pre-post pilot study. Cogn Behav Neurol25, 121–127.
154.
GadientRA, OttenUH (1997) Interleukin-6 (IL-6)–a molecule with both beneficial and destructive potentials. Prog Neurobiol52, 379–390.
SoaresJZ, ValeurJ, Saltyte BenthJ, KnapskogAB, SelbaekG, BogdanovicN, PettersenR (2022) Associations between intrathecal levels of vitamin d, cytokines, and core biomarkers of Alzheimer’s disease: A cross-sectional study. J Alzheimers Dis89, 825–834.
157.
ShultzTD, FoxJ, HeathH3rd, KumarR (1983) Do tissues other than the kidney produce 1,25-dihydroxyvitamin D3 in vivo? A reexamination. Proc Natl Acad Sci U S A80, 1746–1750.
158.
StubbsJR, IdicullaA, SlusserJ, MenardR, QuarlesLD (2010) Cholecalciferol supplementation alters calcitriol-responsive monocyte proteins and decreases inflammatory cytokines in ESRD. J Am Soc Nephrol21, 353–361.
159.
EylesDW, SmithS, KinobeR, HewisonM, McGrathJJ (2005) Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat29, 21–30.
160.
MedeirosJFP, de Oliveira BorgesMV, SoaresAA, Dos SantosJC, de OliveiraABB, da CostaCHB, CruzMS, BortolinRH, de FreitasRCC, DantasPMS, HirataMH, SilbigerVN, LuchessiAD (2020) The impact of vitamin D supplementation on VDR gene expression and body composition in monozygotic twins: Randomized controlled trial. Sci Rep10, 11943.
161.
CampbellMJ (2014) Vitamin D and the RNA transcriptome: More than mRNA regulation. Front Physiol5, 181.
162.
LeeSM, PikeJW (2016) The vitamin D receptor functions as a transcription regulator in the absence of 1,25-dihydroxyvitamin D(3). J Steroid Biochem Mol Biol164, 265–270.
163.
WangF, MarshallCB, IkuraM (2013) Transcriptional/epigenetic regulator CBP/p300 in tumorigenesis: Structural and functional versatility in target recognition. Cell Mol Life Sci70, 3989–4008.
164.
WangJ, HuoK, MaL, TangL, LiD, HuangX, YuanY, LiC, WangW, GuanW, ChenH, JinC, WeiJ, ZhangW, YangY, LiuQ, ZhouY, ZhangC, WuZ, XuW, ZhangY, LiuT, YuD, ChenL, ZhuD, ZhongX, KangL, GanX, YuX, MaQ, YanJ, ZhouL, LiuZ, ZhuY, ZhouT, HeF, YangX (2011) Toward an understanding of the protein interaction network of the human liver. Mol Syst Biol7, 536.
165.
BaudinoTA, KraichelyDM, JefcoatSCJr, WinchesterSK, PartridgeNC, MacDonaldPN (1998) Isolation and characterization of a novel coactivator protein, NCoA-62, involved in vitamin D-mediated transcription. J Biol Chem273, 16434–16441.
166.
DespouyG, BastieJN, DeshaiesS, BalitrandN, MazharianA, Rochette-EglyC, ChomienneC, DelvaL (2003) Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II. J Biol Chem278, 6355–6362.
HsiehJC, SiskJM, JurutkaPW, HausslerCA, SlaterSA, HausslerMR, ThompsonCC (2003) Physical and functional interaction between the vitamin D receptor and hairless corepressor, two proteins required for hair cycling. J Biol Chem278, 38665–38674.
169.
RamagopalanSV, HegerA, BerlangaAJ, MaugeriNJ, LincolnMR, BurrellA, HandunnetthiL, HandelAE, DisantoG, OrtonSM, WatsonCT, MorahanJM, GiovannoniG, PontingCP, EbersGC, KnightJC (2010) A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution. Genome Res20, 1352–1360.
MeyerMB, GoetschPD, PikeJW (2012) VDR/RXR and TCF4/beta-catenin cistromes in colonic cells of colorectal tumor origin: Imact on c-FOS and c-MYC gene expression. Mol Endocrinol26, 37–51.
172.
DingN, YuRT, SubramaniamN, ShermanMH, WilsonC, RaoR, LeblancM, CoulterS, HeM, ScottC, LauSL, AtkinsAR, BarishGD, GuntonJE, LiddleC, DownesM, EvansRM (2013) A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response. Cell153, 601–613.
173.
FleetJC (2004) Rapid, membrane-initiated actions of 1,25 dihydroxyvitamin D: What are they and what do they mean?J Nutr134, 3215–3218.
174.
ChenJ, DoroudiM, CheungJ, GrozierAL, SchwartzZ, BoyanBD (2013) Plasma membrane Pdia3 and VDR interact to elicit rapid responses to 1alpha,25(OH)(2)D(3). Cell Signal25, 2362–2373.
175.
AndreuCI, WoehlbierU, TorresM, HetzC (2012) Protein disulfide isomerases in neurodegeneration: From disease mechanisms to biomedical applications. FEBS Lett586, 2826–2834.
GalliganJJ, PetersenDR (2012) The human protein disulfide isomerase gene family. Hum Genomics6, 6.
178.
DursunE, Gezen-AkD (2017) Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin. PLoS One12, e0188605.
179.
EricksonRR, DunningLM, OlsonDA, CohenSJ, DavisAT, WoodWG, KratzkeRA, HoltzmanJL (2005) In cerebrospinal fluid ER chaperones ERp57 and calreticulin bind beta-amyloid. Biochem Biophys Res Commun332, 50–57.
180.
SelivanovaA, WinbladB, DantumaNP, FarmeryMR (2007) Biogenesis and processing of the amyloid precursor protein in the early secretory pathway. Biochem Biophys Res Commun357, 1034–1039.
181.
ShiX, LuX, ZhanL, LiuL, SunM, GongX, SuiH, NiuX, LiuS, ZhengL, ChenJ, ZhouY (2011) Rat hippocampal proteomic alterations following intrahippocampal injection of amyloid beta peptide (1-40). Neurosci Lett500, 87–91.
182.
ShenL, ChenC, YangA, ChenY, LiuQ, NiJ (2015) Redox proteomics identification of specifically carbonylated proteins in the hippocampi of triple transgenic Alzheimer’s disease mice at its earliest pathological stage. J Proteomics123, 101–113.
183.
CassanoT, GiamoganteF, CalcagniniS, RomanoA, LavecchiaAM, IngleseF, PagliaG, BukkeVN, RomanoAD, FriuliM, AltieriF, GaetaniS (2023) PDIA3 expression is altered in the limbic brain regions of triple-transgenic mouse model of Alzheimer’s disease. Int J Mol Sci24, 3005.
BaiX, MaiM, YaoK, ZhangM, HuangY, ZhangW, GuoX, XuY, ZhangY, QurbanA, DuanL, BuJ, ZhangJ, WuJ, ZhaoY, YuanX, ZuH (2022) The role of DHCR24 in the pathogenesis of AD: Re-cognition of the relationship between cholesterol and AD pathogenesis. Acta Neuropathol Commun10, 35.
186.
Genaro-MattosTC, AndersonA, AllenLB, KoradeZ, MirnicsK (2019) Cholesterol biosynthesis and uptake in developing neurons. ACS Chem Neurosci10, 3671–3681.
187.
BrownAJ, IkonenE, OlkkonenVM (2014) Cholesterol precursors: More than mere markers of biosynthesis. Curr Opin Lipidol25, 133–139.
188.
FunfschillingU, JockuschWJ, SivakumarN, MobiusW, CorthalsK, LiS, QuintesS, KimY, SchaapIA, RheeJS, NaveKA, SaherG (2012) Critical time window of neuronal cholesterol synthesis during neurite outgrowth. J Neurosci32, 7632–7645.
189.
Tsui-PierchalaBA, EncinasM, MilbrandtJ, JohnsonEMJr (2002) Lipid rafts in neuronal signaling and function. Trends Neurosci25, 412–417.
190.
KimuraE, TohyamaC (2017) Embryonic and postnatal expression of aryl hydrocarbon receptor mRNA in mouse brain. Front Neuroanat11, 4.
191.
HuangX, Powell-CoffmanJA, JinY (2004) The AHR-1 aryl hydrocarbon receptor and its co-factor the AHA-1 aryl hydrocarbon receptor nuclear translocator specify GABAergic neuron cell fate in C. elegans. Development131, 819–828.
192.
QinH, Powell-CoffmanJA (2004) The Caenorhabditis elegans aryl hydrocarbon receptor, AHR-1, regulates neuronal development. Dev Biol270, 64–75.
193.
KimMD, JanLY, JanYN (2006) The bHLH-PAS protein Spineless is necessary for the diversification of dendrite morphology of Drosophila dendritic arborization neurons. Genes Dev20, 2806–2819.
BrinkmannV, Ale-AghaN, HaendelerJ, VenturaN (2019) The aryl hydrocarbon receptor (AhR) in the aging process: Another puzzling role for this highly conserved transcription factor. Front Physiol10, 1561.
196.
ChristofiC, LamnisL, StarkA, PalmH, RomerK, VogtT, ReichrathJ (2022) Cross-talk of aryl hydrocarbon receptor (AHR)- and vitamin D receptor (VDR)-signaling in Human keratinocytes. Anticancer Res42, 5049–5067.
197.
SlominskiAT, KimTK, QayyumS, SongY, JanjetovicZ, OakASW, SlominskiRM, RamanC, StefanJ, Mier-AguilarCA, AtigaddaV, CrossmanDK, GolubA, BilokinY, TangEKY, ChenJY, TuckeyRC, JettenAM, SongY (2021) Vitamin D and lumisterol derivatives can act on liver X receptors (LXRs). Sci Rep11, 8002.
LiX, ZhongH, WangZ, XiaoR, AntonsonP, LiuT, WuC, ZouJ, WangL, NalvarteI, XuH, WarnerM, GustafssonJA, FanX (2021) Loss of liver X receptor beta in astrocytes leads to anxiety-like behaviors via regulating synaptic transmission in the medial prefrontal cortex in mice. Mol Psychiatry26, 6380–6393.
200.
JonathanMC, AdrianSH, GonzaloA (2021) Type II nuclear receptors with potential role in Alzheimer disease. Mol Aspects Med78, 100940.
201.
SutherlandMK, SomervilleMJ, YoongLK, BergeronC, HausslerMR, McLachlanDR (1992) Reduction of vitamin D hormone receptor mRNA levels in Alzheimer as compared to Huntington hippocampus: Correlation with calbindin-28k mRNA levels. Brain Res Mol Brain Res13, 239–250.
202.
PodusloSE, YinX (2001) Chromosome 12 and late onset Alzheimer’s disease. Neurosci Lett310, 188–190.
HollenbachE, AckermannS, HymanBT, RebeckGW (1998) Confirmation of an association between a polymorphism in exon 3 of the low-density lipoprotein receptor-related protein gene and Alzheimer’s disease. Neurology50, 1905–1907.
205.
Luedecking-ZimmerE, DeKoskyS, NebesR, KambohI (2003) Association of the 3’UTR transcription factor LBP-1c/CP2/LSF polymorphism with late-onset Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet117B, 114–117.
206.
Gezen-AkD, DursunE, ErtanT, HanagasiH, GurvitH, EmreM, EkerE, OzturkM, EnginF, YilmazerS (2007) Association between vitamin D receptor gene polymorphism and Alzheimer’s disease. Tohoku J Exp Med212, 275–282.
207.
LehmannDJ, RefsumH, WardenDR, MedwayC, WilcockGK, SmithDA (2011) The vitamin D receptor gene is associated with Alzheimer’s disease.79-. Neurosci Let504, 82.
208.
BeechamGW, MartinER, LiYJ, SliferMA, GilbertJR, HainesJL, Pericak-VanceMA (2009) Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. Am J Hum Genet84, 35–43.
209.
BeydounMA, DingEL, BeydounHA, TanakaT, FerrucciL, ZondermanAB (2012) Vitamin D receptor and megalin gene polymorphisms and their associations with longitudinal cognitive change in US adults. Am J Clin Nutr95, 163–178.
210.
BeydounMA, TajuddinSM, DoreGA, CanasJA, BeydounHA, EvansMK, ZondermanAB (2017) Vitamin D receptor and megalin gene polymorphisms are associated with longitudinal cognitive change among African-American urban adults. J Nutr147, 1048–1062.
211.
Gezen-AkD, DursunE, BilgicB, HanagasiH, ErtanT, GurvitH, EmreM, EkerE, UlutinT, UysalO, YilmazerS (2012) Vitamin D receptor gene haplotype is associated with late-onset Alzheimer’s disease. Tohoku J Exp Med228, 189–196.
212.
AlayliogluM, DursunE, GencG, SengulB, BilgicB, GunduzA, ApaydinH, KiziltanG, GurvitH, HanagasiH, Oztop CakmakO, ErtanS, YilmazerS, Gezen-AkD (2022) Genetic variants of vitamin D metabolism-related DHCR7/NADSYN1 locus and CYP2R1 gene are associated with clinical features of Parkinson’s disease. Int J Neurosci132, 439–449.
213.
LarssonSC, TraylorM, MarkusHS, MichaelssonK (2018) Serum parathyroid hormone, 25-Hydroxyvitamin D, and risk of Alzheimer’s disease: A Mendelian randomization study. Nutrients10, 1243.
214.
MokryLE, RossS, MorrisJA, ManousakiD, ForgettaV, RichardsJB (2016) Genetically decreased vitamin D and risk of Alzheimer disease. Neurology87, 2567–2574.
215.
BrewerLD, ThibaultV, ChenKC, LangubMC, LandfieldPW, PorterNM (2001) Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons. J Neurosci21, 98–108.
GrimmMOW, ThielA, LauerAA, WinklerJ, LehmannJ, RegnerL, NelkeC, JanitschkeD, BenoistC, StreidenbergerO, StotzelH, EndresK, HerrC, BeisswengerC, GrimmHS, BalsR, LammertF, HartmannT (2017) Vitamin D and its analogues decrease amyloid-beta (Abeta) formation and increase abeta-degradation. Int J Mol Sci18, 2764.
219.
LandelV, StephanD, CuiX, EylesD, FeronF (2018) Differential expression of vitamin D-associated enzymes and receptors in brain cell subtypes. J Steroid Biochem Mol Biol177, 129–134.
220.
BerridgeMJ (2017) Vitamin D and depression: Cellular and regulatory mechanisms. Pharmacol Rev69, 80–92.
221.
MizwickiMT, NormanAW (2009) The vitamin D sterol-vitamin D receptor ensemble model offers unique insights into both genomic and rapid-response signaling.re. Sci Signal2, 4.
222.
MorelloM, LandelV, LacassagneE, BarangerK, AnnweilerC, FeronF, MilletP (2018) Vitamin D improves neurogenesis and cognition in a mouse model of Alzheimer’s disease. Mol Neurobiol55, 6463–6479.
223.
DoreyE, Bamji-MirzaM, NajemD, LiY, LiuH, CallaghanD, WalkerD, LueLF, StanimirovicD, ZhangW (2017) Apolipoprotein E isoforms differentially regulate Alzheimer’s disease and amyloid-beta-induced inflammatory response in vivo and in vitro. J Alzheimers Dis57, 1265–1279.
224.
AlamC, HoqueMT, FinnellRH, GoldmanID, BendayanR (2017) Regulation of reduced folate carrier (RFC) by vitamin D receptor at the blood-brain barrier. Mol Pharm14, 3848–3858.
225.
KimH, ShinJY, LeeYS, YunSP, MaengHJ, LeeY (2020) Brain endothelial P-glycoprotein level is reduced in Parkinson’s disease via a vitamin D receptor-dependent pathway. Int J Mol Sci21, 8538.
YanMH, WangX, ZhuX (2013) Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radic Biol Med62, 90–101.
228.
MaoP, ReddyPH (2011) Aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction in Alzheimer’s disease: Implications for early intervention and therapeutics. Biochim Biophys Acta1812, 1359–1370.
229.
KukrejaL, KujothGC, ProllaTA, Van LeuvenF, VassarR (2014) Increased mtDNA mutations with aging promotes amyloid accumulation and brain atrophy in the APP/Ld transgenic mouse model of Alzheimer’s disease. Mol Neurodegener9, 16.
230.
ManczakM, ParkBS, JungY, ReddyPH (2004) Differential expression of oxidative phosphorylation genes in patients with Alzheimer’s disease: Implications for early mitochondrial dysfunction and oxidative damage. Neuromolecular Med5, 147–162.
231.
LunnonK, KeohaneA, PidsleyR, NewhouseS, Riddoch-ContrerasJ, ThubronEB, DevallM, SoininenH, KloszewskaI, MecocciP, TsolakiM, VellasB, SchalkwykL, DobsonR, MalikAN, PowellJ, LovestoneS, HodgesA, AddNeuroMed Consortium
(2017) Mitochondrial genes are altered in blood early in Alzheimer’s disease. Neurobiol Aging53, 36–47.
232.
Gezen-AkD, AlayliogluM, GencG, SengulB, KeskinE, SorduP, GulecZEK, ApaydinH, Bayram-GurelC, UlutinT, YilmazerS, ErtanS, DursunE (2020) Altered transcriptional profile of mitochondrial DNA-encoded OXPHOS subunits, mitochondria quality control genes, and intracellular ATP levels in blood samples of patients with Parkinson’s disease. J Alzheimers Dis74, 287–307.
233.
AlmerasL, EylesD, BenechP, LaffiteD, VillardC, PatatianA, BoucrautJ, Mackay-SimA, McGrathJ, FeronF (2007) Developmental vitamin D deficiency alters brain protein expression in the adult rat: Implications for neuropsychiatric disorders. Proteomics7, 769–780.
234.
DzikKP, KaczorJJ (2019) Mechanisms of vitamin D on skeletal muscle function: Oxidative stress, energy metabolism and anabolic state. Eur J Appl Physiol119, 825–839.
235.
RyanZC, CraigTA, FolmesCD, WangX, LanzaIR, SchaibleNS, SalisburyJL, NairKS, TerzicA, SieckGC, KumarR (2016) 1alpha,25-Dihydroxyvitamin D3 regulates mitochondrial oxygen consumption and dynamics in human skeletal muscle cells. J Biol Chem291, 1514–1528.
236.
LeeCT, WangJY, ChouKY, HsuMI (2019) 1,25-Dihydroxyvitamin D3 modulates the effects of sublethal BPA on mitochondrial function via activating PI3K-Akt pathway and 17beta-estradiol secretion in rat granulosa cells. J Steroid Biochem Mol Biol185, 200–211.
237.
McGrathJ, IwazakiT, EylesD, BurneT, CuiX, KoP, MatsumotoI (2008) Protein expression in the nucleus accumbens of rats exposed to developmental vitamin D deficiency. PLoS One3, e2383.
238.
SilvagnoF, De VivoE, AttanasioA, GalloV, MazzuccoG, PescarmonaG (2010) Mitochondrial localization of vitamin D receptor in human platelets and differentiated megakaryocytes. PLoS One5, e8670.
239.
SilvagnoF, ConsiglioM, FoglizzoV, DestefanisM, PescarmonaG (2013) Mitochondrial translocation of vitamin D receptor is mediated by the permeability transition pore in human keratinocyte cell line. PLoS One8, e54716.
240.
RiccaC, AillonA, BergandiL, AlottoD, CastagnoliC, SilvagnoF (2018) Vitamin D receptor is necessary for mitochondrial function and cell health. Int J Mol Sci19, 1672.
241.
Gezen-AkD, AlayliogluM, YurttasZ, CamogluT, SengulB, IslerC, Yasar KinaU, KeskinE, AtasoyIL, KafardarAM, UzanM, AnnweilerC, DursunE (2023) Vitamin D receptor regulates transcription of mitochondrial DNA and directly interacts with mitochondrial DNA and TFAM. J Nutr Biochem116, 109322.
242.
CapiatiD, BenassatiS, BolandRL (2002) 1,25(OH)2-vitamin D3 induces translocation of the vitamin D receptor (VDR) to the plasma membrane in skeletal muscle cells. J Cell Biochem86, 128–135.
243.
NormanAW, MizwickiMT, NormanDP (2004) Steroid-hormone rapid actions, membrane receptors and a conformational ensemble model. Nat Rev Drug Discov3, 27–41.
KhmelevaSA, RadkoSP, KozinSA, KiselevaYY, MezentsevYV, MitkevichVA, KurbatovLK, IvanovAS, MakarovAA (2016) Zinc-mediated binding of nucleic acids to amyloid-beta aggregates: Role of histidine residues. J Alzheimers Dis54, 809–819.
249.
BaileyJA, MaloneyB, GeYW, LahiriDK (2011) Functional activity of the novel Alzheimer’s amyloid beta-peptide interacting domain (AbetaID) in the APP and BACE1 promoter sequences and implications in activating apoptotic genes and in amyloidogenesis. Gene488, 13–22.
250.
MaloneyB, LahiriDK (2011) The Alzheimer’s amyloid beta-peptide (Abeta) binds a specific DNA Abeta-interacting domain (AbetaID) in the APP, BACE1, and APOE promoters in a sequence-specific manner: Characterizing a new regulatory motif. Gene488, 1–12.
PalmerHG, LarribaMJ, GarciaJM, Ordonez-MoranP, PenaC, PeiroS, PuigI, RodriguezR, de la FuenteR, BernadA, PollanM, BonillaF, GamalloC, de HerrerosAG, MunozA (2004) The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer. Nat Med10, 917–919.
253.
PenaC, GarciaJM, GarciaV, SilvaJ, DominguezG, RodriguezR, MaximianoC, Garcia de HerrerosA, MunozA, BonillaF (2006) The expression levels of the transcriptional regulators p300 and CtBP modulate the correlations between SNAIL, ZEB1, E-cadherin and vitamin D receptor in human colon carcinomas. Int J Cancer119, 2098–2104.
254.
DanielC, SchroderO, ZahnN, GaschottT, SteinhilberD, SteinJM (2007) The TGFbeta/Smad 3-signaling pathway is involved in butyrate-mediated vitamin D receptor (VDR)-expression. J Cell Biochem102, 1420–1431.
255.
GiladLA, BreslerT, GnainskyJ, SmirnoffP, SchwartzB (2005) Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells. J Endocrinol185, 577–592.
256.
PanYZ, GaoW, YuAM (2009) MicroRNAs regulate CYP3A4 expression via direct and indirect targeting. Drug Metab Dispos37, 2112–2117.
257.
LinYC, HsiehLC, KuoMW, YuJ, KuoHH, LoWL, LinRJ, YuAL, LiWH (2007) Human TRIM71 and its nematode homologue are targets of let-7 microRNA and its zebrafish orthologue is essential for development. Mol Biol Evol24, 2525–2534.
258.
MohriT, NakajimaM, TakagiS, KomagataS, YokoiT (2009) MicroRNA regulates human vitamin D receptor. Int J Cancer125, 1328–1333.
259.
HelwakA, KudlaG, DudnakovaT, TollerveyD (2013) Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell153, 654–665.
260.
LechnerD, KallayE, CrossHS (2007) 1alpha,25-dihydroxyvitamin D3 downregulates CYP27B1 and induces CYP24A1 in colon cells. Mol Cell Endocrinol263, 55–64.
DursunE, CandasE, YilmazerS, Gezen-AkD (2019) Amyloid beta 1-42 alters the expression of miRNAs in cortical neurons. J Mol Neurosci67, 181–192.
263.
KomagataS, NakajimaM, TakagiS, MohriT, TaniyaT, YokoiT (2009) Human CYP24 catalyzing the inactivation of calcitriol is post-transcriptionally regulated by miR-125b. Mol Pharmacol76, 702–709.
264.
GeorgesSA, BieryMC, KimSY, SchelterJM, GuoJ, ChangAN, JacksonAL, CarletonMO, LinsleyPS, ClearyMA, ChauBN (2008) Coordinated regulation of cell cycle transcripts by p53-Inducible microRNAs, miR-192 and miR-215. Cancer Res68, 10105–10112.
BurneTH, JohnstonAN, McGrathJJ, Mackay-SimA (2006) Swimming behaviour and post-swimming activity in Vitamin D receptor knockout mice. Brain Res Bull69, 74–78.
KivimakiM, LuukkonenR, BattyGD, FerrieJE, PenttiJ, NybergST, ShipleyMJ, AlfredssonL, FranssonEI, GoldbergM, KnutssonA, KoskenvuoM, KuosmaE, NordinM, SuominenSB, TheorellT, VuoksimaaE, WesterholmP, WesterlundH, ZinsM, KivipeltoM, VahteraJ, KaprioJ, Singh-ManouxA, JokelaM (2018) Body mass index and risk of dementia: Analysis of individual-level data from 1.3 million individuals. Alzheimers Dement14, 601–609.
269.
BraakH, ThalDR, GhebremedhinE, Del TrediciK (2011) Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years. J Neuropathol Exp Neurol70, 960–969.
270.
HillAB (1965) The environment and disease: Association or causation?Proc R Soc Med58, 295–300.
271.
ChakkeraM, RaviN, RamarajuR, VatsA, NairAR, BandhuAK, KoiralaD, PallapothuMR, Quintana MarinezMG, KhanS (2022) The efficacy of vitamin D supplementation in patients with Alzheimer’s disease in preventing cognitive decline: A systematic review. Cureus14, e31710.
272.
AliA, ShahSA, ZamanN, UddinMN, KhanW, AliA, RiazM, KamilA (2021) Vitamin D exerts neuroprotection via SIRT1/nrf-2/ NF-kB signaling pathways against D-galactose-induced memory impairment in adult mice. Neurochem Int142, 104893.
273.
BaoZ, WangX, LiY, FengF (2020) Vitamin D alleviates cognitive dysfunction by activating the VDR/ERK1/2 signaling pathway in an Alzheimer’s disease mouse model. Neuroimmunomodulation27, 178–185.
274.
BennettL, KersaitisC, MacaulaySL, MunchG, NiedermayerG, NigroJ, PayneM, SheeanP, VallottonP, ZabarasD, BirdM (2013) Vitamin D2-enriched button mushroom (Agaricus bisporus) improves memory in both wild type and APPswe/PS1dE9 transgenic mice. PLoS One8, e76362.
275.
FanYG, GuoT, HanXR, LiuJL, CaiYT, XueH, HuangXS, LiYC, WangZY, GuoC (2019) Paricalcitol accelerates BACE1 lysosomal degradation and inhibits calpain-1 dependent neuronal loss in APP/PS1 transgenic mice. EBioMedicine45, 393–407.
276.
GuoYX, HeLY, ZhangM, WangF, LiuF, PengWX (2016) 1,25-Dihydroxyvitamin D3 regulates expression of LRP1 and RAGE in vitro and in vivo, enhancing Abeta1-40 brain-to-blood efflux and peripheral uptake transport. Neuroscience322, 28–38.
277.
KangJ, ParkM, LeeE, JungJ, KimT (2022) The role of vitamin D in Alzheimer’s disease: A transcriptional regulator of amyloidopathy and gliopathy. Biomedicines10, 1824.
278.
KhairyEY, AttiaMM (2021) Protective effects of vitamin D on neurophysiologic alterations in brain aging: Role of brain-derived neurotrophic factor (BDNF). Nutr Neurosci24, 650–659.
279.
LaiRH, HsuCC, YuBH, LoYR, HsuYY, ChenMH, JuangJL (2022) Vitamin D supplementation worsens Alzheimer’s progression: Animal model and human cohort studies. Aging Cell21, e13670.
280.
MedhatE, RashedL, AbdelgwadM, AboulhodaBE, KhalifaMM, El-DinSS (2020) Exercise enhances the effectiveness of vitamin D therapy in rats with Alzheimer’s disease: Emphasis on oxidative stress and inflammation. Metab Brain Dis35, 111–120.
281.
MehrabadiS, SadrSS (2020) Administration of Vitamin D(3) and E supplements reduces neuronal loss and oxidative stress in a model of rats with Alzheimer’s disease. Neurol Res42, 862–868.
282.
MehriN, HaddadiR, GanjiM, ShahidiS, Soleimani AslS, Taheri AzandarianiM, RanjbarA (2020) Effects of vitamin D in an animal model of Alzheimer’s disease: Behavioral assessment with biochemical investigation of Hippocampus and serum. Metab Brain Dis35, 263–274.
283.
PierucciF, Garcia-GilM, FratiA, BiniF, MartinesiM, VanniniE, MainardiM, LuzzatiF, PerettoP, CaleoM, MeacciE (2017) Vitamin D(3) protects against Abeta peptide cytotoxicity in differentiated human neuroblastoma SH- SY5Y cells: A role for S1P1/p38MAPK/ATF4 axis. Neuropharmacology116, 328–342.
284.
Saad El-DinS, RashedL, MedhatE, Emad AboulhodaB, Desoky BadawyA, Mohammed ShamsEldeenA, AbdelgwadM (2020) Active form of vitamin D analogue mitigates neurodegenerative changes in Alzheimer’s disease in rats by targeting Keap1/Nrf2 and MAPK-38p/ERK signaling pathways. Steroids156, 108586.
285.
WuTY, ZhaoLX, ZhangYH, FanYG (2022) Activation of vitamin D receptor inhibits Tau phosphorylation is associated with reduction of iron accumulation in APP/PS1 transgenic mice. Neurochem Int153, 105260.
286.
YaminiP, RayRS, ChopraK (2018) Vitamin D(3) attenuates cognitive deficits and neuroinflammatory responses in ICV-STZ induced sporadic Alzheimer’s disease. Inflammopharmacology26, 39–55.
287.
LiL, LiWJ, ZhengXR, LiuQL, DuQ, LaiYJ, LiuSQ (2022) Eriodictyol ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via vitamin D receptor-mediated Nrf2 activation. Mol Med28, 11.
288.
PikeJW, MeyerMB, BenkuskyNA, LeeSM, St JohnH, CarlsonA, OnalM, ShamsuzzamanS (2016) Genomic determinants of vitamin D-regulated gene expression. Vitam Horm100, 21–44.
289.
LinR (2016) Crosstalk between vitamin D metabolism, VDR signalling, and innate immunity. Biomed Res Int2016, 1375858.
290.
ZmijewskiMA, CarlbergC (2020) Vitamin D receptor(s): In the nucleus but also at membranes?Exp Dermatol29, 876–884.
