title: Autophagy and Its Comprehensive Impact on ALS.
abstract: Autophagy is a degradative modality that involves intracellular elimination of proteins and organelles by lysosomes. It is a conservative process and plays a crucial role in cell growth and development, and keeping cellular homeostasis especially under stress-induced situations. Recently, increasing evidence suggests that autophagic alternations may contribute to amyotrophic lateral sclerosis (ALS) as one of initial factors. LC3-II and p62 are found increased in spinal cord of both ALS patients and experimental models, indicating overwhelming autophagic level. But the aggregation of ALS-associated proteins, including SOD1 and TDP-43 suggest possible insufficiency of autophagy induction. Besides, augment autophagic level through genetic pathway or rapamycin leads to paradoxical results in different neurodegenerative diseases models. So, it remains controversial about autophagic effects on ALS progress. In this review, we will depict a comprehensive role that autophagy plays in ALS and focus on the influence of impaired autophagic flux and excessive autophagic vacuoles (AVs) that may aggregate ALS development. And we will discuss the potential therapeutic targets through modulating autophagic level to treat this disease.
authors: Department of Neurology, Central South University, Changsha, Hunan, People's Republic of China.
authors: Cheng-yuan
authors: CY
authors: Song
authors: Ji-feng
authors: JF
authors: Guo
authors: Yuan
authors: Y
authors: Liu
authors: Bei-sha
authors: BS
authors: Tang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D020123:Sirolimus / Q000633:toxicity; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D007166:Immunosuppressive Agents; D008869:Microtubule-Associated Proteins; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D020123:Sirolimus