Long non-coding RNA NEAT1_1 ameliorates TDP-43 toxicity in in vivo models of TDP-43 proteinopathy. Issue 11 (2nd November 2021)

• Record Type: Journal Article
• Authors: Matsukawa, Koji; Kukharsky, Michail S.; Park, Sei-Kyoung; Park, Sangeun; Watanabe, Naruaki; Iwatsubo, Takeshi; Hashimoto, Tadafumi; Liebman, Susan W.; Shelkovnikova, Tatyana A.
• Is Part Of: RNA biology. Volume 18:Issue 11(2021)
• Page Start: 1546
• Page End: 1554
• Publication Date: 2021-11-02
• Subjects: TDP-43 -- NEAT1 -- FUS -- FTLD -- frontotemporal dementia -- Alzheimer's disease -- ALS -- neurodegeneration -- proteinopathy -- drosophila -- yeast; RNA -- Periodicals; Molecular biology -- Periodicals; Molecular biology; RNA; Periodicals; 572.8805
• DOI: 10.1080/15476286.2020.1860580
• Languages: English
• ISSNs: 1547-6286

Abstract

ABSTRACT: 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.