title: Calcium dyshomeostasis and neurotoxicity of Alzheimer's beta-amyloid protein.
abstract: Neurotoxicity of Alzheimer's beta-amyloid protein (AbetaP) is central to the pathogenesis of Alzheimer's disease (AD). Recent approaches have emphasized the importance of AbetaP oligomerization, which causes synaptic degeneration and neuronal loss, finally leading to the pathogenesis of AD. Although the precise molecular mechanism of AbetaP neurotoxicity remains elusive, our and other numerous findings have demonstrated that AbetaP directly incorporated into neuronal membranes formed calcium-permeable ion channels (amyloid channels) and resulted in an abnormal elevation of the intracellular calcium levels. The formation of amyloid channels and the abnormal increase of intracellular Ca(2+) have also been commonly observed in other neurodegenerative diseases, including conformational diseases such as prion disease or dementia with Lewy bodies. This article reviews the current understanding of the pathology of AD based on the hypothesis that the disruption of calcium homeostasis through amyloid channels may be the molecular basis of AbetaP neurotoxicity. The potential development of preventive agents is also discussed.
authors.affiliation: Department of Analytical Chemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Nobeoka-shi, Miyazaki, Japan. kawamasa@phoenix.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawahara
authors.forename: Midori
authors.initials: M
authors.lastname: Negishi-Kato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sadakane
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D005104:Expert Testimony; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008954:Models, Biological
chemical_list: D016229:Amyloid beta-Peptides; D015220:Calcium Channels; D002118:Calcium