Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2022.020
Sinapic Acid Ameliorates REV-ERB α Modulated Mitochondrial Fission against MPTP-Induced Parkinson’s Disease Model
Sang-Bin Lee1,2 and Hyun Ok Yang1,*
1Department of Integrative Biological Sciences and Industry, Sejong University, Seoul 05006, 2School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
*E-mail: hoyang@sejong.ac.kr
Tel: +82-2-3408-1959, Fax: +82-2-3408-4336
Received: February 7, 2022; Revised: March 29, 2022; Accepted: April 26, 2022; Published online: May 25, 2022.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, and accumulating evidence indicates that mitochondrial dysfunction is associated with progressive deterioration in PD patients. Previous studies have shown that sinapic acid has a neuroprotective effect, but its mechanisms of action remain unclear. The neuroprotective effect of sinapic acid was assayed in a PD mouse model generated by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as well as in SH-SY5Y cells. Target protein expression was detected by western blotting. Sinapic acid treatment attenuated the behavioral defects and loss of dopaminergic neurons in the PD models. Sinapic acid also improved mitochondrial function in the PD models. MPTP treatment increased the abundance of mitochondrial fission proteins such as dynamin-related protein 1 (Drp1) and phospho-Drp1 Ser616. In addition, MPTP decreased the expression of the REV-ERB α protein. These changes were attenuated by sinapic acid treatment. We used the pharmacological REV-ERB α inhibitor SR8278 to confirmation of protective effect of sinapic acid. Treatment of SR8278 with sinapic acid reversed the protein expression of phospho-Drp1 Ser616 and REV-ERB α on MPTP-treated mice. Our findings demonstrated that sinapic acid protects against MPTP-induced PD and these effects might be related to the inhibiting abnormal mitochondrial fission through REV-ERB α.
Keywords: Parkinson disease, Sinapic acid, Mitochondrial fission, MPTP, REB-ERB α


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