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Long non-coding RNA NEAT1_1 ameliorates TDP-43 toxicity in in vivo models of TDP-43 proteinopathy

Matsukawa, Koji, Kukharsky, Michail S, Park, Si-Kyoung, Park, Sangeun, Watanabe, Naruaki, Iwatsubo, Takeshi, Hashimoto, Tadafumi, Liebman, Susan W and Shelkovnikova, Tatyana 2021. Long non-coding RNA NEAT1_1 ameliorates TDP-43 toxicity in in vivo models of TDP-43 proteinopathy. RNA Biology 10.1080/15476286.2020.1860580
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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. KEYWORDS: TDP-43NEAT1FUSFTLDfrontotemporal dementiaAlzheimer’s diseaseALSneurodegeneration

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Biosciences
Publisher: Taylor & Francis
ISSN: 1547-6286
Date of First Compliant Deposit: 7 December 2020
Date of Acceptance: 3 December 2020
Last Modified: 04 Feb 2021 01:54

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