Role of A
and the
7 nicotinic acetylcholine receptor in regulating synaptic plasticity in Alzheimers disease
Authors: David H. Small1; Lisa R. Fodero2; Dusan Losic3; Cindy Chu4; Marie-Isabel Aguilar5; Lisandra L. Martin6; Mary Chebib4
Source: Letters in Peptide Science, Volume 10, Number 5, 2003 , pp. 401-404(4)
Publisher: Springer
Abstract:
Alzheimers disease (AD) is caused by the accumulation of
-amyloid protein (A
) in the brain. The aggregation of
-amyloid protein to higher molecular weight fibrillar forms is also considered to be an important step in the pathogenesis of the disease. The memory problems associated with AD are likely to be caused by changes in synaptic plasticity. Recent studies suggest that A
binds to the
7 nicotinic acetylcholine receptor (
7 nAChR), which plays an important role in synaptic plasticity and memory. A loop domain localized towards the C-terminus of the extracellular region of the receptor has been identified as forming part of a putative A
-binding site. In cell culture experiments, the binding of A
to the
7 nAChR has been found to cause an increase in the level of acetylcholinesterase, which is also increased around amyloid plaques in the AD brain. These studies indicate that the A
-binding site on the
7 nAChR receptor is an important new target for therapeutic development in AD.
Keywords: Alzheimers disease; amyloid; atomic force microscopy; nicotinic; synaptic plasticity
Document Type: Research article
DOI: 10.1007/s10989-004-2390-y
Affiliations: 1: Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia (), Email: david.small@med.monash.edu.au 2: Department of Pathology, University of Melbourne, Victoria, Parkville, 3052, Australia 3: School of Chemistry Physics & Earth Sciences, Flinders University of South Australia, SA, 5042, Australia 4: Faculty of Pharmacy, University of Sydney, NSW, Australia 5: Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia 6: School of Chemistry, Monash University, Victoria, 3800, Australia

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