Role of autophagy in the pathogenesis of multiple sclerosis

• Published in: Neuroscience bulletin Vol. 31; no. 4; pp. 435 - 444
• Main Authors: Liang, Peizhou, Le, Weidong
• Format: Journal Article
• Language: English
• Published: Shanghai Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 01-08-2015
• Subjects: Anatomy; Anesthesiology; Animals; Autophagy; Biomedical and Life Sciences; Biomedicine; Encephalitis - metabolism; Encephalitis - physiopathology; Human Physiology; Humans; Immunity, Innate; Mitochondria - physiology; Multiple Sclerosis - physiopathology; Neuroglia - physiology; Neurology; Neurosciences; Pain Medicine; Review; 中枢神经系统; 发病机制; 多发性硬化; 炎症反应; 神经胶质细胞; 细胞存活; 自噬作用; 自身免疫性疾病; neuro-inflammation; multiple sclerosis; autophagy
• ISSN: 1673-7067; 1995-8218
• DOI: 10.1007/s12264-015-1545-5

Autophagy plays an important role in maintaining the cellular homeostasis. One of its functions is to degrade unnecessary organelles and proteins for energy recycling or amino-acids for cell survival. Ablation of autophagy leads to neurodegeneration. Multiple sclerosis （MS）, a permanent neurological impairment typical of chronic inflammatory demyelinating disorder, is an auto-immune disease of the central nervous system （CNS）. Autophagy is tightly linked to the innate and adaptive immune systems during the autoimmune process, and several studies have shown that autophagy directly participates in the progress of MS or experimental autoimmune encephalomyelitis （EAE, a mouse model of MS）. Dysfunction of mitochondria that intensively influences the autophagy pathway is one of the important factors in the pathogenesis of MS. Autophagy-related gene （ATG） 5 and immune-related GTPase M （IRGM） 1 are increased, while ATG16L2 is decreased, in T-cells in EAE and active relapsing-remitting MS brains. Administration of rapamycin, an inhibitor of mammalian target of rapamycin （mTOR）, ameliorates relapsing-remitting EAE. Inflammation and oxidative stress are increased in MS lesions and EAE, but Lamp2 and the LC3-11/LC3-1 ratio are decreased. Furthermore, autophagy in various glial cells plays important roles in regulating neuro-inflammation in the CNS, implying potential roles in MS. In this review, we discuss the role of autophagy in the peripheral immune system and the CNS in neuroinflammation associated with the pathogenesis of MS.