| Abstract: |
Oligomeric assemblies of tau and the RNA-binding proteins (RBPs) Musashi (MSI) are reported in Alzheimer’s disease (AD). However, the role of MSI and tau interaction in their aggregation process and its effects are nor clearly known in neurodegenerative diseases. Here, we investigated the expression and cellular localization of MSI1 and MSI2 in the brains tissues of Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) as well as in the wild-type mice and tau knock-out and P301L tau mouse models. We observed that formation of pathologically relevant protein inclusions was driven by the aberrant interactions between MSI and tau in the nuclei associated with age-dependent extracellular depositions of tau/MSI complexes. Furthermore, tau and MSI interactions induced impairment of nuclear/cytoplasm transport, chromatin remodeling and nuclear lamina formation. Our findings provide mechanistic insight for pathological accumulation of MSI/tau aggregates providing a potential basis for therapeutic interventions in neurodegenerative proteinopathies. © 2020, The Author(s). |
| Keywords: |
immunohistochemistry; controlled study; protein expression; protein phosphorylation; aged; aged, 80 and over; middle aged; human cell; genetics; protein localization; mass spectrometry; mouse; animal; cytology; metabolism; animals; mice; mus; gene expression; nerve tissue proteins; protein; small interfering rna; protein binding; immunofluorescence; pathology; immunoreactivity; transgenic mouse; mice, transgenic; disease model; rna binding protein; rna; rna-binding proteins; nucleocytoplasmic transport; genetic transfection; brain; brain development; western blotting; immunoprecipitation; immunoblotting; cellular distribution; cytoplasm; active transport, cell nucleus; rodent; cell nucleus; high performance liquid chromatography; disease models, animal; frontal lobe; rna processing; tetracycline; nerve protein; alzheimer disease; degenerative disease; rna extraction; chromatin assembly and disassembly; tau protein; neurodegenerative diseases; cell; amyloid beta protein; protein aggregation; hek293 cells; cell inclusion; inclusion bodies; liquid chromatography-mass spectrometry; autofluorescence; amyotrophic lateral sclerosis; nuclear pore complex; ribonucleoprotein; tau proteins; fourier transform; very elderly; humans; human; male; female; article; hek293 cell line; rna-binding domain; cell cycle assay; protein aggregate; mapt protein, human; msi1 protein, human; msi2 protein, human; subgranular zone; protein aggregates
|
