title: SMAD Transcription Factor, Sma-9, Attunes TGF-β Signaling Cascade Towards Modulating Amyloid Beta Aggregation and Associated Outcome in Transgenic C. elegans.
abstract: The considerable roles of transcription factors, and the associated signaling molecules that activate them, are well deciphered in the context of various biological processes. One of the important transcription factors, the transforming growth factor-β (TGF-β) pathway, has a profound role in neuronal cell survival-a process that gets awry in multiple conditions which include various neurological ailments. Alzheimer's disease (AD) is one such condition wherein toxic buildup of misfolded proteins occurs, cellular signaling gets disrupted, and neuronal cell death ensues. We endeavored to study whether the transcriptional cofactors, associated with the TGF-β pathway, have a role to play in modulating the disease outcome. Employing transgenic C. elegans model, we studied β-amyloid aggregation, acetylcholine levels, and associated endpoints and figured that SMAD transcriptional cofactor, Sma-9, modulates the outcome associated with AD. Our studies conclude that Sma-9, a subset of the TGF-β-mediated signaling pathway, can be a potential target in neurodegenerative AD as it can influence neuronal, and organismal, survival and play crucial role in limiting adverse effects of AD.
authors.affiliation: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226 031, U.P., India.
authors.forename: Rizwanul
authors.initials: R
authors.lastname: Haque
authors.affiliation: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226 031, U.P., India. anazir@cdri.res.in.
authors.forename: Aamir
authors.initials: A
authors.lastname: Nazir
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C483687:Sma-9 protein, C elegans; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
keywords: Aging; Alzheimer’s disease; C. elegans; Neurodegenerative disease; Sma-9; TGF-β