Salidroside protects dopaminergic neurons by regulating the mitochondrial MEF2D-ND6 pathway in the MPTP/MPP+ -induced model of Parkinson's disease.

Abstract

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.

• Authors: Tao Li, Wei Zhang, Xiaogang Kang, Ruixin Yang, Ruru Li, Lu Huang, Jianzong Chen, Qian Yang, Xiaolong Sun
• Journal: Journal of neurochemistry (J Neurochem) Vol. 153 Issue 2 Pg. 276-289 (04 2020) ISSN: 1471-4159 [Electronic] England
• PMID: 31520529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 International Society for Neurochemistry.

Chemical References

• Glucosides
• MEF2 Transcription Factors
• Mef2d protein, mouse
• Neuroprotective Agents
• Phenols
• NADH Dehydrogenase
• NADH dehydrogenase subunit 6, mouse
• rhodioloside

Topics

• Animals
• Cell Survival (drug effects)
• Dopaminergic Neurons (drug effects, metabolism)
• Glucosides (pharmacology)
• MEF2 Transcription Factors (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mitochondria (drug effects, metabolism)
• NADH Dehydrogenase (metabolism)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Parkinsonian Disorders (metabolism)
• Phenols (pharmacology)
• Signal Transduction (drug effects)