loading page

Neuroprotective effect of sinapic acid on REV-ERB α modulated mitochondrial fission in Parkinson’s disease
  • Sang-Bin LEE,
  • Hyun Ok Yang
Sang-Bin LEE
Korea Institute of Science and Technology
Author Profile
Hyun Ok Yang
Korea Institute of Science and Technology
Author Profile

Abstract

Background and Purpose Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, and accumulating evidence indicates that mitochondrial dysfunction is associated with the progressive deterioration of this disease. Previous studies have shown that sinapic acid has a neuroprotective effect, but its mechanisms of action remain unclear. Experimental Approach 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 and immunofluorescence. Key Results Sinapic acid treatment attenuated the behavioural defects and loss of dopaminergic neurons in the MPTP mouse model of PD. Sinapic acid also improved mitochondrial function in MPTP-treated mice, as indicated by diminished mitochondrial swelling and increased mitochondrial glutamate dehydrogenase activity. MPTP treatment increased the abundance of mitochondrial fission proteins such as dynamin-related protein 1 (Drp1) and phospho-Drp1 Ser616, while sinapic acid treatment attenuated abnormal mitochondrial fission. In addition, MPTP decreased the expression of REV-ERB α protein, whereas sinapic acid increased its expression. To elucidate the molecular mechanism linking REV-ERB α and mitochondrial fission, we used the pharmacological REV-ERB α inhibitor SR8278. Sinapic acid and SR8278 co-treatment reversed phospho-Drp1 Ser616 protein expression and the protective effect of sinapic acid in MPTP-treated mice. Conclusion and Implications Our findings demonstrated that sinapic acid protects against MPTP-induced PD by inhibiting abnormal mitochondrial fission through REV-ERB α.