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Salidroside protects dopaminergic neurons by regulating the mitochondrial MEF2D‐ND6 pathway in the MPTP/MPP + ‐induced model of Parkinson's disease
Author(s) -
Li Tao,
Zhang Wei,
Kang Xiaogang,
Yang Ruixin,
Li Ruru,
Huang Lu,
Chen Jianzong,
Yang Qian,
Sun Xiaolong
Publication year - 2020
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14868
Subject(s) - mptp , salidroside , neuroprotection , oxidative stress , mitochondrion , dopaminergic , microbiology and biotechnology , biology , pink1 , apoptosis , pharmacology , chemistry , biochemistry , neuroscience , dopamine , autophagy , mitophagy
Mitochondrial complex I damage and oxidative stress play critical roles in the degeneration of dopaminergic (DA) neurons during the progression of Parkinson’s disease (PD). Our previous study showed that NADH dehydrogenase 6 (ND6), exclusively regulated by mitochondrial myocyte enhancer factor 2D (MEF2D), was critical for mitochondrial complex I assembly. Recently, we found that Salidroside (Sal), isolated from Rhodiola rosea L., protected DA neurons by regulating oxidative stress‐related mitochondrial pathways. Here, we investigated whether the mitochondrial MEF2D‐ND6 pathway was involved in the neuroprotective effects of Sal. Our results showed that in 1‐methyl‐4‐phenylpyridinium (MPP + )‐injured SN4741 cells, Sal pretreatment improved cellular viability, inhibited apoptosis, and restored both the mitochondrial membrane potential and complex I activity. Similarly, the protective effects of Sal on mitochondrial complex I activity, DA neurons, and behavior were also confirmed in 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP)‐lesioned mice. Besides, Sal pretreatment restored the expression of mitochondrial MEF2D and ND6 in MPP + ‐injured SN4741 cells and MPTP‐lesioned mice. Finally and interestingly, the protective effects of Sal were not observed in cells transfected with Mt2Ddn, a specific blocker of mitochondrial MEF2D function, suggesting that Sal protects DA neurons primarily by regulating the mitochondrial MEF2D‐ND6 pathway. 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.