title: [Conformational change, pore formation and neurotoxicity of amyloidogenic proteins].
abstract: Conformational changes of Alzheimer's beta-amyloid protein (AbetaP) enhance its neurotoxicity, and finally lead to Alzheimer's pathogenesis. Recent studies have suggested that a common mechanism is based on the diverse diseases termed "conformational diseases", including other neurodegenerative diseases such as prion diseases, Parkinson's disease, and triplet-repeat disease. These diseases share similarity in the formation of beta-sheet containing amyloid fibrils by disease-related proteins including prion protein, alpha-synuclein, polyglutamine, and the introduction of apoptotic degeneration. We have investigated the conformational changes of AbetaP and its neurotoxicity and found that trace metals including aluminum enhanced the aggregation of AbetaP. Although the molecular mechanism of neurodegeneration induced by these conformational disease-related proteins remains elusive, these proteins have the ability to directly incorporate into membranes directly and to form calcium-permeable ion channels. Our and other numerous studies have revealed that AbetaP caused the abnormal elevation of intracellular calcium levels. We review here the current understanding of the pathology of the conformational diseases based on the hypothesis that the disruption of calcium homeostasis through amyloid channels may be the molecular basis of the neurotoxicity of AbetaP and other disease-related proteins.
authors.affiliation: Department of Analytical Chemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Miyazaki.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawahara
mesh_terms: D000371:Agglutination; D000535:Aluminum; D000544:Alzheimer Disease / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D006706:Homeostasis; D006801:Humans; D011487:Protein Conformation
chemical_list: D016229:Amyloid beta-Peptides; D000535:Aluminum; D002118:Calcium