Amyloid beta peptides and glutamatergic synaptic dysregulation.

Abstract:

:Alzheimer's disease (AD) is a major neurodegenerative disorder in which overproduction and accumulation of amyloid beta (Abeta) peptides result in synaptic dysfunction. Recent reports strongly suggest that in the initial stages of AD glutamate receptors are dysregulated by Abeta accumulation resulting in disruption of glutamatergic synaptic transmission which parallels early cognitive deficits. In the presence of Abeta, 2-amino-3-(3-hydoxy-5-methylisoxazol-4-yl) propionic acid (AMPA) glutamate receptor function is disrupted and the surface expression is reduced. Abeta has also been shown to modulate N-methyl-d-aspartate receptors (NMDARs) and metabotropic glutamate receptors. The Abeta mediated glutamate receptor modifications can lead to synaptic dysfunction resulting in excitotoxic neurodegeneration during the progression of AD. This review discusses the recent findings that glutamatergic signaling could be compromised by Abeta induced modulation of synaptic glutamate receptors in specific brain regions.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Parameshwaran K,Dhanasekaran M,Suppiramaniam V

doi

10.1016/j.expneurol.2007.10.008

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

7-13

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(07)00391-3

journal_volume

210

pub_type

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