title: Cellular levels of Grb2 and cytoskeleton stability are correlated in a neurodegenerative scenario.
abstract: Alzheimer's disease (AD) manifests as neuronal loss. On the premise 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 β-amyloid oligomers and intracellular elevation of amyloid precursor protein intracellular domain levels, have been used to closely inspect the series of signalling events. In their presence, multiple signalling pathways involving ROCK and PAK1 proteins lead to disassembly of the cytoskeleton, and Grb2 partially counterbalances the cytoskeletal loss. Increased Grb2-NOX4 interactions play a preventive role against cytoskeletal disassembly, in turn blocking the activity of nitrogen oxides 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.
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhannagar, Kolkata, West Bengal 700064, India.
authors.forename: Piyali
authors.initials: P
authors.lastname: Majumder
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhannagar, Kolkata, West Bengal 700064, India.
authors.forename: Kasturi
authors.initials: K
authors.lastname: Roy
authors.affiliation: Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon 122 050, India.
authors.forename: Brijesh Kumar
authors.initials: BK
authors.lastname: Singh
authors.affiliation: Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon 122 050, India.
authors.forename: Nihar Ranjan
authors.initials: NR
authors.lastname: Jana
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhannagar, Kolkata, West Bengal 700064, India debashis.mukhopadhyay@saha.ac.in.
authors.forename: Debashis
authors.identifier: 0000-0002-4516-2260
authors.initials: D
authors.lastname: Mukhopadhyay
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D051380:GRB2 Adaptor Protein / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D000074663:NADPH Oxidase 4 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D003598:Cytoskeletal Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D000074663:NADPH Oxidase 4; C498910:NOX4 protein, human
keywords: AICD; APP/PS1 mouse model; Alzheimer's disease; Cytoskeleton; GRB2; Growth factor receptor bound protein 2; β-amyloid; β-amyloid protein precursor intracellular domain