Protective roles for induction of autophagy in multiple proteinopathies.
Many late-onset neurodegenerative diseases, including Parkinson's disease, tauopathies, Huntington's disease and forms of spinocerebellar ataxia, are caused by aggregate-prone proteins. Previously we showed that mutant huntingtin is an autophagy substrate and that autophagy induction reduced soluble and aggregated huntingtin levels and attenuated its toxicity in cell, fly and mouse models of disease. We have recently shown in cell and fly models that autophagy induction may have general protective effects across a range of diseases caused by aggregate-prone intracellular proteins. First, we showed that this strategy reduces the levels of the primary toxin, the aggregate-prone mutant protein. Second, our recent work suggests that autophagy induction may have additional cytoprotective effects by protecting cells against a range of subsequent pro-apoptotic insults.
Menzies
Fiona M
FM
Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK.
Ravikumar
Brinda
B
Rubinsztein
David C
DC
D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology
D020123:Sirolimus