Alzheimer's Disease (AD) manifests neuronal loss. On the premises of Grb2 overexpression in AD mouse brain and brain tissues of AD patients, our study primarily focuses on the stability of cytoskeletal proteins in the context of degenerative AD like conditions. Two predominant molecular features of AD, extracellular accumulation of Aβ oligomers and intracellular elevation of AICD levels, have been used to closely inspect the series of signaling events. In their presence, multiple signaling pathways involving ROCK and PAK1 proteins lead to disassembly of the cytoskeleton and Grb2 partially counterbalances the cytoskeletal loss. Increased Grb2-NOX4 interaction plays a preventive role against cytoskeletal disassembly, in turn blocking NOX activity and decreasing the expression of slingshot homolog 1 (SSH-1) protein, a potent inducer of cytoskeleton disassembly. This study unravels a unique role of Grb2 in protecting the cytoskeletal architecture in AD like conditions and presents a potential new strategy for controlling neurodegeneration.
- Received September 8, 2016.
- Accepted March 28, 2017.
- © 2017. Published by The Company of Biologists Ltd
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