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

Brent L. Kelly, Robert Vassar, Adriana Ferreira*

*Corresponding author for this work

Research output: Contribution to journalArticle

109 Scopus citations

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 β-amyloid (Aβ), 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 Aβ-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 Aβ-induced decrease in dynamin I was likely the result of a calpain-mediated cleavage of dynamin 1 protein and possibly the down-regulation of dynamic, 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.

Original languageEnglish (US)
Pages (from-to)31746-31753
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number36
DOIs
StatePublished - Sep 9 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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