Glutathione (GSH) is an important endogenous antioxidant protecting cells from oxidative injury. Cysteine (Cys), the substrate limiting the production of GSH, is mainly generated from the trans-sulfuration pathway. S-adenosylmethionine (SAM) is a critical molecule produced in the methionine cycle and can be utilized by the trans-sulfuration pathway. Reductions in GSH and SAM as well as dysfunction in the trans-sulfuration pathway have been documented in the brains of Alzheimer’s disease (AD) patients. Our previous in vivo study revealed that SAM administration attenuated oxidative stress induced by amyloid-β (Aβ) through the enhancement of GSH.
Objective:
To investigate the effect of Aβ-induced oxidative stress on the trans-sulfuration pathway in astrocytes and neurons, respectively, and the protective effect of SAM on neurons.
Methods:
APP/PS1 transgenic mice and the primary cultured astrocytes, neurons, and HT22 cells were used in the current study.
Results:
SAM could rescue the low trans-sulfuration pathway activity induced by Aβ only in astrocytes, accompanying with increasing levels of Cys and GSH. The decrease of cellular viability of neurons caused by Aβ was greatly reversed when co-cultured with astrocytes with SAM intervention. Meanwhile, SAM improved cognitive performance in APP/PS1 mice.
Conclusion:
In terms of astrocyte protection from oxidative stress, SAM might be a potent antioxidant in the therapy of AD patients.
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