Protein misfolding, amyloid formation, and neurodegeneration: a critical role for molecular chaperones?
The most conspicuous feature of many neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's disease, is the occurrence of protein aggregates in ordered fibrillar structures known as amyloid found inside and outside of brain cells. The appearance of aggregates in diseased brains implies an underlying incapacity in the cellular machinery of molecular chaperones that normally functions to prevent the accumulation of misfolded proteins. Here we review recent studies that have revealed a critical role for molecular chaperones in several neurodegenerative disorders.
Department of Pharmacology, University of Washington, Seattle 98195, USA. mucho@u.washington.edu
Paul J
PJ
Muchowski
D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding
D000682:Amyloid; D018832:Molecular Chaperones; D010455:Peptides; C097188:polyglutamine