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Tau protein modulates an epigenetic mechanism of cellular senescence in human SH-SY5Y neuroblastoma cells

Authors :
Claudia Magrin
Martina Bellafante
Martina Sola
Ester Piovesana
Marco Bolis
Luciano Cascione
Sara Napoli
Andrea Rinaldi
Stéphanie Papin
Paolo Paganetti
Source :
Frontiers in Cell and Developmental Biology, Vol 11 (2023)
Publication Year :
2023
Publisher :
Frontiers Media S.A., 2023.

Abstract

Introduction: Progressive Tau deposition in neurofibrillary tangles and neuropil threads is the hallmark of tauopathies, a disorder group that includes Alzheimer’s disease. Since Tau is a microtubule-associated protein, a prevalent concept to explain the pathogenesis of tauopathies is that abnormal Tau modification contributes to dissociation from microtubules, assembly into multimeric β-sheets, proteotoxicity, neuronal dysfunction and cell loss. Tau also localizes in the cell nucleus and evidence supports an emerging function of Tau in DNA stability and epigenetic modulation.Methods: To better characterize the possible role of Tau in regulation of chromatin compaction and subsequent gene expression, we performed a bioinformatics analysis of transcriptome data obtained from Tau-depleted human neuroblastoma cells.Results: Among the transcripts deregulated in a Tau-dependent manner, we found an enrichment of target genes for the polycomb repressive complex 2. We further describe decreased cellular amounts of the core components of the polycomb repressive complex 2 and lower histone 3 trimethylation in Tau deficient cells. Among the de-repressed polycomb repressive complex 2 target gene products, IGFBP3 protein was found to be linked to increased senescence induction in Tau-deficient cells.Discussion: Our findings propose a mechanism for Tau-dependent epigenetic modulation of cell senescence, a key event in pathologic aging.

Details

Language :
English
ISSN :
2296634X
Volume :
11
Database :
Directory of Open Access Journals
Journal :
Frontiers in Cell and Developmental Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.38cfccd2d5e4432fafa2b6cbdfe9a046
Document Type :
article
Full Text :
https://doi.org/10.3389/fcell.2023.1232963