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The Role of Aβ-Induced Calcium Dysregulation in the Pathogenesis of Alzheimer's Disease

Citation

Small, DH and Gasperini, R and Vincent, AJ and Hung, AC and Foa, L, The Role of Aβ-Induced Calcium Dysregulation in the Pathogenesis of Alzheimer's Disease, Journal of Alzheimer's Disease, 16, (2) pp. 225-233. ISSN 1387-2877 (2009) [Refereed Article]

DOI: doi:10.3233/JAD-2009-0951

Abstract

Although many of the biochemical mechanisms which regulate production or clearance of the amyloid-‚ protein (A‚)of Alzheimerís disease (AD) are now well understood, the mechanism of A‚ neurotoxicity remains unclear. A number of studies have shown that A‚ can disrupt neuronal Ca2+ homeostasis by inducing influx of extracellular Ca2+ into the neuronal cytoplasm. Ca2+ is known to play an important role in neuronal excitability, synaptic plasticity and neurotoxicity. Therefore, A‚-induced Ca2+ dysregulation may contribute to many of the cognitive and neuropathologic features of AD. In vitro studies show that A‚ can increase ion permeability in lipid membranes. This increased permeability is reportedly associated with the formation of artificial ion pores formed from A‚ oligomers. However, a number of other studies show that A‚ can activate endogenous ion channels on the cell surface. There is also increasing evidence that presenilin mutations alter intracellular Ca2+ stores. It is likely that elucidation of the mechanism by which A‚ and presenilin cause Ca2+ dysregulation in neurons will help to identify new drug targets for the treatment of AD.

Item Details

Item Type:Refereed Article
Keywords:Alzheimerís disease, amyloid, calcium, neurotoxicity, synaptic plasticity
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Small, DH (Professor David Small)
Author:Gasperini, R (Dr Rob Gasperini)
Author:Vincent, AJ (Dr Adele Vincent)
Author:Hung, AC (Dr Amos Hung)
Author:Foa, L (Professor Lisa Foa)
ID Code:60244
Year Published:2009
Web of Science® Times Cited:45
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-01-27
Last Modified:2011-07-28
Downloads:0

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