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