Understanding synaptic events that precede nerve cell death

Jane Sullivan, PhD
University of Washington (Seattle, WA)
Year Awarded:
2007
Grant Duration:
April 1, 2007 to March 31, 2010
Disease:
Alzheimer's Disease
Award Amount:
$149,950
Grant Reference ID:
A2007348
Award Type:
Pilot
Award Region:
US Northwestern

Role of Presenilin in Synaptic Transmission

Summary

Identifying specific changes in synaptic function produced by mutant presenilin, a protein strongly implicated in the inherited form of Alzheimer's disease, will provide molecular targets for novel therapies to improve cognitive function and delay further neurodegeneration in patients with early Alzheimer's disease

Details

The earliest manifestations of Alzheimer's disease are deficiencies in cognitive function, specifically problems with memory. These earliest symptoms of the disease are most likely caused by abnormal synaptic transmission. As the disease progresses and dementia becomes more severe, neurons will die, but the earlier changes, those that are hypothesized to be caused by more subtle effects on the way that synapses operate before neurons die, have not been well studied. This is because these changes are occurring in patients that are still alive, and they cannot be investigated with existing techniques. In order to understand what changes are taking place at synapses before neurons die, a model system must be used. This model system must replicate the changes that are thought to be taking place in the brains of patients with early Alzheimer's disease. This grant proposal describes a series of pilot studies that will develop such a model system using brain cells from mice. Identifying specific changes in synaptic function produced by mutant presenilin, a protein strongly implicated in the inherited form of Alzheimer's disease, will provide molecular targets for novel therapies to improve cognitive function and delay further neurodegeneration in patients with early Alzheimer's disease

Publications

Pratt KG, Zhu P, Watari H, Cook DG, Sullivan JM. J Neurosci. (2011) A novel role for {gamma}-secretase: selective regulation of spontaneous neurotransmitter release from hippocampal neurons. 2011 Jan 19;31(3):899-906. PubMed Icon Google Scholar Icon
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