Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.5.3 (
complex I
)
8,901
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Salidroside protects dopaminergic neurons by regulating the mitochondrial MEF2D-ND6 pathway in the MPTP/MPP
+
-induced model of Parkinson's disease. 3152 May 29
