title: Molecular pathways to polyglutamine aggregation.
abstract: Over 100 human cellular proteins contain a repetitive polyglutamine tract, however, only nine ofthese proteins are associated with disease. In these proteins, the expanded polyQ tract perturbs the native conformation, resulting in an ordered aggregation process that leads to the formation of amyloid-like fibrils. The misfolding pathway involves the formation of prefibrillar oligomeric structures, which are proposed to be involved in cellular toxicity. Non-polyQ host protein regions modulate the misfolding pathway, suggesting an importance ofprotein context in aggregation. This chapter describes the current research regarding polyQ misfolding, with emphasis on the species populated during aggregation, suggesting an important role of protein context in modulating the aggregation pathway.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Robertson
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Bottomley
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D060833:Cellular Microenvironment; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011485:Protein Binding; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D057165:Proteostasis Deficiencies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D012996:Solutions
chemical_list: D000682:Amyloid; D009842:Oligopeptides; D010455:Peptides; D054852:Small Molecule Libraries; D012996:Solutions; C407346:polyglutamine-binding protein 1; C097188:polyglutamine; D002392:Catechin; C045651:epigallocatechin gallate