title: The role of Abeta-induced calcium dysregulation in the pathogenesis of Alzheimer's disease.
abstract: Although many of the biochemical mechanisms which regulate production or clearance of the amyloid-beta protein (Abeta) of Alzheimer's disease (AD) are now well understood, the mechanism of Abeta neurotoxicity remains unclear. A number of studies have shown that Abeta can disrupt neuronal Ca(2+) homeostasis by inducing influx of extracellular Ca(2+) into the neuronal cytoplasm. Ca(2+) is known to play an important role in neuronal excitability, synaptic plasticity and neurotoxicity. Therefore, Abeta-induced Ca(2+) dysregulation may contribute to many of the cognitive and neuropathologic features of AD. In vitro studies show that Abeta can increase ion permeability in lipid membranes. This increased permeability is reportedly associated with the formation of artificial ion pores formed from Abeta oligomers. However, a number of other studies show that Abeta can activate endogenous ion channels on the cell surface. There is also increasing evidence that presenilin mutations alter intracellular Ca(2+) stores. It is likely that elucidation of the mechanism by which Abeta and presenilin cause Ca(2+) dysregulation in neurons will help to identify new drug targets for the treatment of AD.
authors.affiliation: Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia. d.h.small@menzies.utas.edu.au
authors.forename: David H
authors.initials: DH
authors.lastname: Small
authors.forename: Robert
authors.initials: R
authors.lastname: Gasperini
authors.forename: Adele J
authors.initials: AJ
authors.lastname: Vincent
authors.forename: Amos C
authors.initials: AC
authors.lastname: Hung
authors.forename: Lisa
authors.initials: L
authors.lastname: Foa
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects*; D053763:Presenilins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015220:Calcium Channels; D053763:Presenilins; D002118:Calcium