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  • Title: Molecular mechanism of neurodegeneration induced by Alzheimer's beta-amyloid protein: channel formation and disruption of calcium homeostasis.
    Author: Kawahara M, Kuroda Y.
    Journal: Brain Res Bull; 2000 Nov 01; 53(4):389-97. PubMed ID: 11136994.
    Abstract:
    The etiology of Alzheimer's disease has been suggested to be linked to the neurodegeneration induced by beta-amyloid protein (AbetaP), however, the mechanism underlying the latter remains unknown. We have previously shown the direct incorporation of AbetaP into neuronal membranes of immortalized hypothalamic neurons (GT1-7 cells) associated with the formation of calcium-permeable pores, and the elevation of the intracellular calcium concentrations in the GT1-7 cells. Taking together our results and those of numerous other studies, we hypothesize that the disruption of calcium homeostasis by AbetaP-channels may be the molecular basis of the neurotoxicity of AbetaP, and the development of Alzheimer's disease. It is also proposed that the constituents of membrane lipids may play important roles in the process of this channel formation. Our hypothesis may also explain the mechanism of development of other 'conformational diseases', such as prion disease or type 2 diabetes mellitus, which share some common features with Alzheimer's disease.
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