Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 150, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2021.105175
Keywords
ALS; NEAT1; Paraspeckles; C9orf72; Antisense oligonucleotide; Nuclear body
Categories
Funding
- Research Center Network for Realization Research Centers/Projects of Regenerative Medicine (the program for Intractable Disease Research Utilizing Disease-specific iPS Cells) in AMED [JP15bm0609003, JP16bm0609003, JP17bm0609003, JP17bm0804003, JP18bm0804003, JP19bm0804003, JP20bm0804003, JP21bm0804003]
- KAKENHI from the Japan Society for the Promotion of Science [20H00485, 21K07281]
- Grants-in-Aid for Scientific Research [20H00485, 21K07281] Funding Source: KAKEN
Ask authors/readers for more resources
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease caused by factors such as RNA-binding proteins and genetic mutations, which play different roles in different stages; research has found that C9orf72 gene repeat expansion has a significant impact on the pathology of ALS.
Amyotrophic lateral sclerosis (ALS) is a representative neurological disease that is known to devastate entire motor neurons within a period of just a few years. Discoveries of the specific pathologies of relevant RNA-binding proteins, including TAR DNA-binding protein-43 (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS), and the causative genes of both familial and sporadic ALS have provided crucial information that could lead to a cure. In recent ALS research the GGGGCC-repeat expansion in the C9orf72 gene was identified as one of the most important pathological findings, suggesting the significance of both nuclear dysfunction due to dipeptide repeat proteins (DPRs) and RNA toxicity (such as pathological alterations of non-coding RNAs). In research on model animals carrying ALS-related molecules, the determination of whether a factor is protective or toxic has been controversial. Herein, we review the findings regarding NEAT1 RNA and C9orf72 GGGGCC repeats associated with ALS, from the viewpoint of conversion from the protective stage in the nucleus in earlyphase ALS to late-phase induction of cell death. This review will provide insights for the development of RNA effectors as novel ALS treatments.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available