Abstract
Conformational changes of Alzheimers β-amyloid protein (AβP) enhance its neurotoxicity and play important roles in the pathogenesis of Alzheimers disease. Recent studies have suggested that a common mechanism is based on diverse “conformational diseases”. They share similarity in their formation of β-sheet containing amyloid fibrils by disease-related proteins and the introduction of apoptotic degeneration. Numerous studies, including our own, have revealed that AbP and several disease-related proteins are capable of directly incorporating into membranes, forming calcium-permeable ion channels, and causing abnormal elevation of intracellular calcium levels. This article reviews the current understanding of the pathology of conformational diseases based on the hypothesis that the disruption of calcium homeostasis through amyloid channels may form the molecular basis of neurotoxicity of AβP and other disease-related proteins. The roles of membrane lipids and potential development of preventive agents are also discussed.
Keywords: pore, cholesterol, neurotoxicity, prion disease, calcium imaging
Current Alzheimer Research
Title: Disruption of Calcium Homeostasis in the Pathogenesis of Alzheimers Disease and Other Conformational Diseases
Volume: 1 Issue: 2
Author(s): Masahiro Kawahara
Affiliation:
Keywords: pore, cholesterol, neurotoxicity, prion disease, calcium imaging
Abstract: Conformational changes of Alzheimers β-amyloid protein (AβP) enhance its neurotoxicity and play important roles in the pathogenesis of Alzheimers disease. Recent studies have suggested that a common mechanism is based on diverse “conformational diseases”. They share similarity in their formation of β-sheet containing amyloid fibrils by disease-related proteins and the introduction of apoptotic degeneration. Numerous studies, including our own, have revealed that AbP and several disease-related proteins are capable of directly incorporating into membranes, forming calcium-permeable ion channels, and causing abnormal elevation of intracellular calcium levels. This article reviews the current understanding of the pathology of conformational diseases based on the hypothesis that the disruption of calcium homeostasis through amyloid channels may form the molecular basis of neurotoxicity of AβP and other disease-related proteins. The roles of membrane lipids and potential development of preventive agents are also discussed.
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Cite this article as:
Kawahara Masahiro, Disruption of Calcium Homeostasis in the Pathogenesis of Alzheimers Disease and Other Conformational Diseases, Current Alzheimer Research 2004; 1 (2) . https://dx.doi.org/10.2174/1567205043332234
DOI https://dx.doi.org/10.2174/1567205043332234 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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