Melatonin Induces Autophagy in Amyotrophic Lateral Sclerosis Mice via Upregulation of SIRT1

Abstract

Amyotrophic lateral sclerosis (ALS) is the neurodegenerative disease that leads to the motor dysfunction damaged by both upper and lower motor neurons. The etiology and pathogenesis of ALS hasn't completely been understood yet up to now, the current study suggests that autophagy plays an important role in the development of ALS. Meanwhile, melatonin is found to inhibit the progression of ALS. To this end, this study aimed to investigate the potential relation between melatonin and autophagy in ALS. The in vivo model of ALS was established to investigate the effects of melatonin in ALS. The mRNA expressions were performed to detect by RT-qPCR, and the protein levels were tested by western blot and immunofluorescence histochemistry staining. The inflammatory cytokine was applied to detect by ELISA. The results showed that melatonin dose-dependently reversed the ALS-induced survival time shortened, weight loss and rotating rod latency decrease. The expressions of both SIRT1 and Beclin-1 as well as the ratio of LC3II/LC3I were significantly upregulated in the ALS mice, while melatonin reversed the upregulation of both SIRT1 and Beclin-1 expression and LC3II/LC3I ratio in a dose-dependent manner. In contrast, melatonin dose-dependently significantly restored the ALS-induced downregulation of p62. Furthermore, SIRT1 silencing notably reduced the effect of melatonin on Beclin-1, LC3II/LC3I, and p62. Melatonin induced autophagy in the ALS mice via the upregulation of SIRT1. Thus, melatonin might act as a new agent for the treatment of ALS.

Keywords: ALS; Autophagy; Beclin-1; LC3I; LC3II; Melatonin; SIRT1; p62.