Long non-coding RNA NEAT1_1 ameliorates TDP-43 toxicity in in vivo models of TDP-43 proteinopathy
Autor: | Koji Matsukawa, Michail S. Kukharsky, Tadafumi Hashimoto, Sei-Kyoung Park, Naruaki Watanabe, Sangeun Park, Susan W. Liebman, Takeshi Iwatsubo, Tatyana A. Shelkovnikova |
---|---|
Rok vydání: | 2021 |
Předmět: |
TDP-43
yeast frontotemporal dementia Mice Neuroblastoma 0302 clinical medicine TDP-43 Proteinopathy proteinopathy 0303 health sciences Neurodegeneration neurodegeneration Brain Frontotemporal lobar degeneration drosophila Long non-coding RNA Cell biology DNA-Binding Proteins Drosophila melanogaster 030220 oncology & carcinogenesis Toxicity RNA Long Noncoding FTLD Alzheimer’s disease Rapid Communication Frontotemporal dementia NEAT1 Mice Transgenic Saccharomyces cerevisiae Biology Brief Communication 03 medical and health sciences In vivo mental disorders medicine Animals Humans Molecular Biology FUS 030304 developmental biology Amyotrophic Lateral Sclerosis nutritional and metabolic diseases Cell Biology medicine.disease nervous system diseases Mice Inbred C57BL Disease Models Animal nervous system TDP-43 Proteinopathies sense organs ALS |
Zdroj: | RNA Biology article-version (VoR) Version of Record |
ISSN: | 1547-6286 |
DOI: | 10.6084/m9.figshare.13554182 |
Popis: | Pathological changes involving TDP-43 protein (‘TDP-43 proteinopathy’) are typical for several neurodegenerative diseases, including frontotemporal lobar degeneration (FTLD). FTLD-TDP cases are characterized by increased binding of TDP-43 to an abundant lncRNA, NEAT1, in the cortex. However it is unclear whether enhanced TDP-43-NEAT1 interaction represents a protective mechanism. We show that accumulation of human TDP-43 leads to upregulation of the constitutive NEAT1 isoform, NEAT1_1, in cultured cells and in the brains of transgenic mice. Further, we demonstrate that overexpression of NEAT1_1 ameliorates TDP-43 toxicity in Drosophila and yeast models of TDP-43 proteinopathy. Thus, NEAT1_1 upregulation may be protective in TDP-43 proteinopathies affecting the brain. Approaches to boost NEAT1_1 expression in the CNS may prove useful in the treatment of these conditions.\ud \ud KEYWORDS: TDP-43NEAT1FUSFTLDfrontotemporal dementiaAlzheimer’s diseaseALSneurodegeneration |
Databáze: | OpenAIRE |
Externí odkaz: |