Monocarboxylate transporter functions and neuroprotective effects of valproic acid in experimental models of amyotrophic lateral sclerosis
- Authors
- Gyawali, Asmita; Latif, Sana; Choi, Seung-Hye; Hyeon, Seung Jae; Ryu, Hoon; Kang, Young-Sook
- Issue Date
- 10-Jan-2022
- Publisher
- BMC
- Keywords
- Amyotrophic lateral sclerosis; Monocarboxylate transporter 1; Sodium-coupled monocarboxylate transporter; Neuroprotection; Valproic acid
- Citation
- JOURNAL OF BIOMEDICAL SCIENCE, v.29, no.1, pp 1 - 13
- Pages
- 13
- Journal Title
- JOURNAL OF BIOMEDICAL SCIENCE
- Volume
- 29
- Number
- 1
- Start Page
- 1
- End Page
- 13
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/145952
- DOI
- 10.1186/s12929-022-00785-3
- ISSN
- 1021-7770
1423-0127
- Abstract
- Background Amyotrophic lateral sclerosis (ALS) is a devasting neurodegenerative disorder for which no successful therapeutics are available. Valproic acid (VPA), a monocarboxylate derivative, is a known antiepileptic drug and a histone deacetylase inhibitor. Methods To investigate whether monocarboxylate transporter 1 (MCT1) and sodium-coupled MCT1 (SMCT1) are altered in ALS cell and mouse models, a cellular uptake study, quantitative real time polymerase chain reaction and western blot parameters were used. Similarly, whether VPA provides a neuroprotective effect in the wild-type (WT; hSOD1WT) and ALS mutant-type (MT; hSOD1G93A) NSC-34 motor neuron-like cell lines was determined through the cell viability assay. Results [H-3]VPA uptake was dependent on time, pH, sodium and concentration, and the uptake rate was significantly lower in the MT cell line than the WT cell line. Interestingly, two VPA transport systems were expressed, and the VPA uptake was modulated by SMCT substrates/inhibitors in both cell lines. Furthermore, MCT1 and SMCT1 expression was significantly lower in motor neurons of ALS (G93A) model mice than in those of WT mice. Notably, VPA ameliorated glutamate- and hydrogen peroxide-induced neurotoxicity in both the WT and MT ALS cell lines. Conclusions Together, the current findings demonstrate that VPA exhibits a neuroprotective effect regardless of the dysfunction of an MCT in ALS, which could help develop useful therapeutic strategies for ALS.
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