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Vitamin B12 Reduces TDP-43 Toxicity by Alleviating Oxidative Stress and Mitochondrial Dysfunction

Title
Vitamin B12 Reduces TDP-43 Toxicity by Alleviating Oxidative Stress and Mitochondrial Dysfunction
Authors
Jeon, Yu.-Mi.Kwon, YounghwiLee, Shinrye.Kim, SeyeonJo, Myungjin.Lee, Seongsoo.Kim, Sang Ryong.Kim, Kiyoung.Kim, Hyung Jun
DGIST Authors
Jeon, Yu.-Mi.; Kwon, Younghwi; Lee, Shinrye.; Kim, Seyeon; Jo, Myungjin.; Lee, Seongsoo.; Kim, Sang Ryong.; Kim, Kiyoung.; Kim, Hyung Jun
Issue Date
2022-01
Citation
Antioxidants, 11(1)
Type
Article
Author Keywords
Amyotrophic lateral sclerosisDrosophilaMitochondrial dysfunctionOxidative stressTAR DNA-binding protein 43
Keywords
TAR DNA-binding protein 43amyotrophic lateral sclerosisDrosophilamitochondrial dysfunctionoxidative stress
ISSN
2076-3921
Abstract
TAR DNA-binding protein 43 (TDP-43) is a member of an evolutionarily conserved family of heterogeneous nuclear ribonucleoproteins that modulate multiple steps in RNA metabolic processes. Cytoplasmic aggregation of TDP-43 in affected neurons is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Mislocalized and accumulated TDP-43 in the cytoplasm induces mitochondrial dysfunction and reactive oxidative species (ROS) production. Here, we show that TDP-43-and rotenone-in-duced neurotoxicity in the human neuronal cell line SH-SY5Y were attenuated by hydroxocobala-min (Hb, vitamin B12 analog) treatment. Although Hb did not affect the cytoplasmic accumulation of TDP-43, Hb attenuated TDP-43-induced toxicity by reducing oxidative stress and mitochondrial dysfunction. Moreover, a shortened lifespan and motility defects in TDP-43-expressing Drosophila were significantly mitigated by dietary treatment with hydroxocobalamin. Taken together, these findings suggest that oral intake of hydroxocobalamin may be a potential therapeutic intervention for TDP-43-associated proteinopathies. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
URI
http://hdl.handle.net/20.500.11750/16093
DOI
10.3390/antiox11010082
Publisher
MDPI AG
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