Autophagy, a guardian against neurodegeneration.
Autophagy is an intracellular degradation process responsible for the clearance of most long-lived proteins and organelles. Cytoplasmic components are enclosed by double-membrane autophagosomes, which subsequently fuse with lysosomes for degradation. Autophagy dysfunction may contribute to the pathology of various neurodegenerative disorders, which manifest abnormal protein accumulation. As autophagy induction enhances the clearance of aggregate-prone intracytoplasmic proteins that cause neurodegeneration (like mutant huntingtin, tau and ataxin 3) and confers cytoprotective roles in cell and animal models, upregulating autophagy may be a tractable therapeutic strategy for diseases caused by such proteins. Here, we will review the molecular machinery of autophagy and its role in neurodegenerative diseases. Drugs and associated signalling pathways that may be targeted for pharmacological induction of autophagy will also be discussed.
García-Arencibia
Moisés
M
Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, UK.
Hochfeld
Warren E
WE
Toh
Pearl P C
PP
Rubinsztein
David C
DC
D000818:Animals; D001343:Autophagy; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction
D009419:Nerve Tissue Proteins