The role of protein misfolding in the pathogenesis of human diseases.
The ability of proteins to fold into complex three-dimensional shapes is truly amazing. Given the difficulty of the reaction it is perhaps unsurprising that many proteins in vivo are unable to fold correctly. These misfolded proteins are generally recognized by the cell's quality control machinery and dealt with through degradation. However in an increasing number of diseases, such as Huntington's, Alzheimer's and alpha1-antitrypsin deficiency, misfolded protein accumulates both within and outside the cell. This aggregated protein is able to evade the normal cellular responses and in some cases even disable it. In this review we present an overview of protein misfolding and examine recent data which is beginning to reveal the mechanisms by which protein aggregates are toxic to cells.
Ellisdon
Andrew M
AM
Department of Biochemistry and Molecular Biology, PO Box 13D Monash University, Australia, 3800.
Bottomley
Stephen P
SP
D000682:Amyloid / Q000378:metabolism*; D030342:Genetic Diseases, Inborn / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D010455:Peptides / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding
D000682:Amyloid; D010455:Peptides; C097188:polyglutamine