TY - JOUR
T1 - β-amyloid-induced dynamin 1 depletion in hippocampal neurons
T2 - A potential mechanism for early cognitive decline in Alzheimer disease
AU - Kelly, Brent L.
AU - Vassar, Robert
AU - Ferreira, Adriana
PY - 2005/9/9
Y1 - 2005/9/9
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M503259200
DO - 10.1074/jbc.M503259200
M3 - Article
C2 - 16002400
AN - SCOPUS:24744472049
VL - 280
SP - 31746
EP - 31753
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 36
ER -