Neurotoxicity of β-Amyloid Protein: Oligomerization, Channel Formation and Calcium Dyshomeostasis

Author(s): Masahiro Kawahara .

Journal Name: Current Pharmaceutical Design

Volume 16 , Issue 25 , 2010

Abstract:

Numerous studies have indicated that Alzheimers amyloid-β protein (Aβ) causes the degeneration of synapses and neurons, finally inducing the pathogenesis of Alzheimers disease (AD). Recent approaches have emphasized the importance of Aβ oligomerization which enhances its neurotoxicity and synaptotoxicity. Our work as well as other groups research have demonstrated that Aβ oligomers are directly incorporated into neuronal membranes and form calcium-permeable ion channels (amyloid channels). Although the precise molecular mechanism of Aβ neurotoxicity remains elusive, the formation of amyloid channels and the resultant abnormal elevation of the intracellular calcium levels might be the primary event for neurodegeneration, considering that calcium dyshomeostasis triggers various apoptotic pathways. This article reviews the current understanding of AD pathology based on the hypothesis that the disruption of calcium homeostasis through amyloid channels may be the molecular basis of Aβ neurotoxicity. The potential development of preventive agents for new therapeutic targets is also discussed.

Keywords: Oligomerization, synaptotoxicity, zinc, aluminum, neurosteroids, apoptosis, membrane fluidity, Aamyloid-b protein, Alzheimer's disease, Ion channels, Amyloid channels, Neurodegeneration, Dyshomeostasis, Dementia, Memory loss, Senile plaques, Neurofibrillary tangles, Prion disease, Parkinson's disease, Huntington's disease, Presenilins, Ca2+ homeostasis, Chromatography, gel electrophoresis, Atomic force microscopy, Transthyletin, Rifampicin, Curcumin, Aspirin, Polymerization, Ca2+ channels, Xenopus oocytes, Tetrodotoxin, Nifedipine, D-APV, Bicuculline, Chelation therapy, Clioquinol, deferoxamine

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Article Details

VOLUME: 16
ISSUE: 25
Year: 2010
Page: [2779 - 2789]
Pages: 11
DOI: 10.2174/138161210793176545
Price: $58

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