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PMID: 16002400 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Beta-amyloid-induced dynamin 1 depletion in hippocampal neurons. A potential mechanism for early cognitive decline in Alzheimer disease.

The Journal of biological chemistry ·Vol. 280 ·No. 36 ·2005-09-09 ·Pages 31746-53

Kelly BL, Vassar R, Ferreira A

Abstract

Synaptic dysfunction is one of the earliest events in the pathogenesis of Alzheimer disease (AD). However, the molecular mechanisms underlying synaptic defects in AD are largely unknown. We report here that beta-amyloid (Abeta), the main component of senile plaques, induced a significant decrease in dynamin 1, a protein that is essential for synaptic vesicle recycling and, hence, for memory formation and information processing. The Abeta-induced dynamin 1 decrease occurred in the absence of overt synaptic loss and was also observed in the Tg2576 mouse model of AD. In addition, our results provided evidence that the Abeta-induced decrease in dynamin 1 was likely the result of a calpain-mediated cleavage of dynamin 1 protein and possibly the down-regulation of dynamin 1 gene expression. These data suggest a mechanism to explain the early cognitive loss without a major decline in synapse number observed in AD and propose a novel therapeutic target for AD intervention.

MeSH Terms
Alzheimer Disease/metabolism,pathology,physiopathology Amyloid beta-Peptides/genetics,physiology Animals Calpain/metabolism Cells, Cultured Cognition/physiology Disease Models, Animal Dynamin I/biosynthesis,metabolism Hippocampus/metabolism,pathology Mice Mice, Transgenic Neurons/metabolism Rats
Chemicals
Amyloid beta-Peptides Calpain Dynamin I
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kelly Brent L
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Vassar Robert
Ferreira Adriana
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M503259200
Published
2005-09-09
Epub
2005-00-07
Pages
31746-53
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC1364535
Subset
IM
Grants
NIA NIH HHS · AG20506 · United States
NINDS NIH HHS · R01 NS039080 · United States
NIA NIH HHS · T32 AG020506 · United States
NIA NIH HHS · R01AG022560 · United States
NINDS NIH HHS · NS39080 · United States
NIA NIH HHS · R01 AG022560 · United States
External Links
PubMed source DOI: 10.1074/jbc.M503259200 PMC Full Text View journal details
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