Our study sheds light upon the protective role of Sal through targeting the mitochondrial MEF2D-ND6 pathway in regulations of mitochondrial function and DA neuronal viability, providing novel mechanistic insights into the neuroprotective effects of Sal against PD.
Furthermore, using the in vivo PD model of C57BL/6 mice insulted with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we found that intragastrical administration of SU4312 (0.2 and 1 mg/kg) greatly ameliorated Parkinsonian motor defects, and restored protein levels of MEF2D, phosphorylated-Ser473-Akt and phosphorylated-Ser9-GSK3β.
These results indicate that the neuronal survival factor MEF2D is decreased in human and experimental PD, and this decrease is specifically associated with α-synuclein accumulation and aggregation.