Journal article
Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer's disease
Brain research, v 1292
25 Sep 2009
PMID: 19635471
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Synaptic loss underlies the memory deficit of Alzheimer's disease (AD). The molecular mechanism is elusive; however, excitatory synapses organized by the postsynaptic density (PSD) have been used as targets for AD treatment. To identify pathological entities at the synapse in AD, synaptic proteins were screened by quantitative proteomic profiling. The critical proteins were then selected for immunoblot analysis. The glutamate receptors N-methyl-d-aspartate (NMDA) receptor 1 and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor 2 (GluR2) were substantially lost; specifically, the loss of GluR2 was up to 40% at PSD in AD. Shank proteins, the organizers of these glutamate receptors at excitatory synapses, were dramatically altered in AD. The level of Shank2 was increased, whereas the protein level of Shank3 was decreased. Further, the Shank3 protein was modified by ubiquitin, indicating that abnormal activity of the ubiquitin–proteasome system may lead to Shank3 degradation in AD. Our findings suggest that disruption of glutamate receptors at the Shank-postsynaptic platform could contribute to destruction of the PSD which underlies the synaptic dysfunction and loss in AD.
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Details
- Title
- Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer's disease
- Creators
- Yuesong Gong - Drexel UniversityCarol F. Lippa - Drexel UniversityJinghua Zhu - University at Albany, State University of New YorkQishan Lin - University at Albany, State University of New YorkAndrea L. Rosso - Drexel University
- Publication Details
- Brain research, v 1292
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000270482900019
- Scopus ID
- 2-s2.0-69449089052
- Other Identifier
- 991019312462004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences