S-Adenosylmethionine Alleviates Amyloid-β-Induced Neural Injury by Enhancing Trans-Sulfuration Pathway Activity in Astrocytes

Background: 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 transsulfuration 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-beta (A beta) through the enhancement of GSH. Objective: To investigate the effect of A beta-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 A beta only in astrocytes, accompanying with increasing levels of Cys and GSH. The decrease of cellular viability of neurons caused by A beta 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.