title: Degradation of misfolded proteins by autophagy: is it a strategy for Huntington's disease treatment?
abstract: Autophagy is a degradation pathway for long-lived cytoplasmic proteins, protein complexes, or damaged organelles. The accumulation and aggregation of misfolded proteins are hallmarks of several neurodegenerative diseases. Many researchers have reported that autophagy degrades disease-causing misfolded and aggregated proteins, including mutant huntingtin (Htt) in Huntington's disease, mutant synuclein in familial Parkingson's disease, mutant Cu, Zn-Superoxide dismutase (SOD1) in familial amyotrophic lateral sclerosis. In this review, we will bring up new evidence to elucidate the involvement of autophagy in degradation of mutant Htt, discuss the mechanisms regulating the degradation of mutant Htt by autophagy and the therapeutic effects of drugs that enhance autophagy to improve clearance of mutant Htt. We propose that enhancement of autophagy by drugs may be a strategy to treat or retard progression of Huntington's disease.
authors: Department of Pharmacology, Laboratory of Aging and Nervous Diseases, Soochow University School of Pharmaceutical Science, Suzhou, China.
authors: Fang
authors: F
authors: Lin
authors: Department of Pharmacology, Laboratory of Aging and Nervous Diseases, Soochow University School of Pharmaceutical Science, Suzhou, China.
authors: Zheng-Hong
authors: ZH
authors: Qin
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002220:Carbamazepine / Q000627:therapeutic use; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008094:Lithium / Q000627:therapeutic use; D050505:Mutant Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010080:Oxazoles / Q000627:therapeutic use; D010455:Peptides / Q000378:metabolism; D000077769:Rilmenidine; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D014199:Trehalose / Q000627:therapeutic use; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D010080:Oxazoles; D010455:Peptides; C097188:polyglutamine; D002220:Carbamazepine; D014635:Valproic Acid; C401859:temsirolimus; D008094:Lithium; D014199:Trehalose; D000077769:Rilmenidine; D020123:Sirolimus
keywords: Huntington's disease; autophagy; huntingtin; polyglutamine expansion