Review
Nature Reviews Neuroscience 3, 862-872 (November 2002) | doi:10.1038/nrn960
Calcium dyshomeostasis and intracellular signalling in alzheimer's disease
Frank M. LaFerla1 About the author
Abstract
Calcium modulates many neural processes, including synaptic plasticity and apoptosis. Dysregulation of intracellular calcium signalling has been implicated in the pathogenesis of Alzheimer's disease. Increased intracellular calcium elicits the characteristic lesions of this disorder, including the accumulation of amyloid-
, the hyperphosphorylation of TAU and neuronal death. Conversely, neurodegeneration that is induced by amyloid-
or TAU is probably mediated by changes in calcium homeostasis. Disruption of calcium regulation in the endoplasmic reticulum mediates the most significant signal-transduction cascades that are associated with Alzheimer's disease. Moreover, mutations that cause familial Alzheimer's disease have been linked to intracellular calcium signalling pathways. Destabilization of calcium signalling seems to be central to the pathogenesis of Alzheimer's disease, and targeting this process might be therapeutically beneficial.
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Author affiliations
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Laboratory of Molecular Neuropathogenesis, Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Building, Irvine, California 92697, USA.
Email: laferla@uci.edu
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