Neuroprotective effect of sinapic acid on REV-ERB α modulated
mitochondrial fission in Parkinson’s disease
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.