Sestrins (sesn) are highly conserved proteins that play an important neuroprotective role, in part as a consequence of their antioxidative capacity, which prevents reactive oxygen species formation. In this study, we evaluated the concentrations of sesn1 and sesn2 in the serum of 41 Alzheimer’s disease (AD) patients, 27 mild cognitive impairment (MCI), and 60 elderly controls, by surface plasmon resonance, which was validated by using western blot. Moreover, the mRNA level of sestrins in all the study groups was determined by real time polymerase chain reaction. The results showed significant overexpression of serum sesn2 protein and mRNA levels in the AD group compared to MCI and elderly control groups. A difference in serum sesn2 concentration between MCI and the control group was also evident. ROC analysis showed highly sensitive, selective cutoff values for sens2 in the differentiation of AD, MCI, and controls. No significant difference in sesn1 level was observed among the study groups. This study highlights the important role of sesn2 in the progression of the AD, indicating its potential utility as a protein marker in this devastating disease.
KimGH, KimJE, RhieSJ, YoonS (2015) The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol24, 325–340.
2.
WangX, WangW, LiL, PerryG, LeeHG, ZhuX (2014) Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta1842, 1240–1247.
3.
FogartyMP, McCormackRM, NoonanJ, MurphyD, GowranA, CampbellVA (2010) A role for p53 in the beta-amyloid-mediated regulation of the lysosomal system. Neurobiol Aging31, 1774–1786.
4.
SperlingRA, AisenPS, BeckettLA, BennettDA, CraftS, FaganAM, IwatsuboT, JackCRJr, KayeJ, MontineTJ, ParkDC, ReimanEM, RoweCC, SiemersE, SternY, YaffeK, CarrilloMC, ThiesB, Morrison-BogoradM, WagsterMV, PhelpsCH (2011) Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement7, 280–292.
5.
FaganAM, HeadD, ShahAR, MarcusD, MintunM, MorrisJC, HoltzmanDM (2009) Decreased cerebrospinal fluid Abeta(42) correlates with brain atrophy in cognitively normal elderly. Ann Neurol65, 176–183.
6.
BudanovAV, SablinaAA, FeinsteinE, KooninEV, ChumakovPM (2004) Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD.. Science304, 596–600.
7.
LeeJH, BudanovAV, ParkEJ, BirseR, KimTE, PerkinsGA, OcorrK, EllismanMH, BodmerR, BierE, KarinM (2010) Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science327, 1223–1228.
8.
BudanovAV, LeeJH, KarinM (2010) Stressin’ Sestrins take an aging fight. EMBO Mol Med2, 388–400.
9.
ReddyK, CusackCL, NnahIC, KhayatiK, SaqcenaC, HuynhTB, NoggleSA, BallabioA, DobrowolskiR (2016) Dysregulation of nutrient sensing and CLEARance in presenilin deficiency. Cell Rep14, 2166–2179.
10.
BudanovAV (2011) Stress-responsive sestrins link p53 with redox regulation and mammalian target of rapamycin signaling. Antioxid Redox Signal15, 1679–1690.
11.
SkovronskyDM, LeeVM, TrojanowskiJQ (2006) Neurodegenerative diseases: New concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol1, 151–170.
12.
UttaraB, SinghAV, ZamboniP, MahajanRT (2009) Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol7, 65–74.
13.
SoontornniyomkijV, SoontornniyomkijB, MooreDJ, GouauxB, MasliahE, TungS, VintersHV, GrantI, AchimCL (2012) Antioxidant sestrin-2 redistribution to neuronal soma in human immunodeficiency virus-associated neurocognitive disorders. J Neuroimmune Pharmacol7, 579–590.
14.
MatheuA, MaraverA, KlattP, FloresI, Garcia-CaoI, BorrasC, FloresJM, ViñaJ, BlascoMA, SerranoM (2007) Delayed ageing through damage protection by the Arf/p53 pathway. Nature448, 375–379.
FreitasS, SimõesMR, AlvesL, SantanaI (2013) Montreal cognitive assessment: Validation study for mild cognitive impairment and Alzheimer disease. Alzheimer Dis Assoc Disord27, 37–43.
18.
GanguliM, RatcliffG, ChandraV, SharmaS, GilbyJ, PandavR, BelleS, RyanC, BakerC, SeabergE, DekoskyS (1995) A Hindi version of the MMSE: The development of a cognitive screening instrument for a largely illeterate rural elderly population in India. Int J Geriatr Psychiatry10, 367–377.
19.
McKhannG, DrachmanD, FolsteinM, KatzmanR, PriceD, StadlanEM (1984) Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease.. Neurology34, 939–944.
20.
O’BryantSE, GuptaV, HenriksenK, EdwardsM, JerominA, ListaS, BazenetC, SoaresH, LovestoneS, HampelH, MontineT, BlennowK, ForoudT, CarrilloM, Graff-RadfordN, LaskeC, BretelerM, ShawL, TrojanowskiJQ, SchupfN, RissmanRA, FaganAM, OberoiP, UmekR, WeinerMW, GrammasP, PosnerH, MartinsR, STAR-B, working BBBIG, Groups (2015) Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer’s disease research. Alzheimers Dement11, 549–560.
21.
PrinceM, WimoA, GuerchetM, AliG-C, WuY-T, PrinaM (2015) World Alzheimer Report: 2015, The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International. World Alzheimer report: 2015.
22.
BudanovAV, KarinM (2008) p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell134, 451–460.
23.
PieperR, GatlinCL, MakuskyAJ, RussoPS, SchatzCR, MillerSS, SuQ, McGrathAM, EstockMA, ParmarPP, ZhaoM, HuangST, ZhouJ, WangF, Esquer-BlascoR, AndersonNL, TaylorJ, SteinerS (2003) The human serum proteome: Display of nearly 3700 chromatographically separated protein spots on two-dimensional electrophoresis gels and identification of 325 distinct proteins. Proteomics3, 1345–1364.
24.
TaylorWH (1969) Serum enzymes in the diagnosis of disease.. Br J Anaesth41, 227–234.
AndersonNL, AndersonNG (2002) The human plasma proteome: History, character, and diagnostic prospects. Mol Cell Proteomics1, 845–867.
27.
ChenYS, ChenSD, WuCL, HuangSS, YangDI (2014) Induction of sestrin2 as an endogenous protective mechanism against amyloid beta-peptide neurotoxicity in primary cortical culture. Exp Neurol253, 63–71.
