Nervonic acid alleviates MPTP-induced Parkinson's disease via MEK/ERK pathway

Cell Mol Biol (Noisy-le-grand). 2024 Apr 28;70(4):100-106. doi: 10.14715/cmb/2024.70.4.16.

Abstract

Nervonic acid (NA) is a primary long-chain fatty acid and has been confirmed to have neuroprotective effects in neurologic diseases. Oxidative stress and neuronal damage are the main causes of Parkinson's disease (PD). This study mainly explored whether NA is involved in regulating oxidative stress and apoptosis in MPTP-induced mouse model and MPP-induced cell model. Through behavior tests, we proved that MPTP-induced motor dysfunction in mice was recovered by NA treatment. NA can reduce MPTP-induced neuronal damage, manifested by elevated levels of TH and dopamine, as well as decreased levels of α-syn. In the in vitro model, we observed from CCK8 assay and flow cytometry that the induction of MPP markedly suppressed cell activity and enhanced cell apoptosis, but these functions were all reversed by NA. Furthermore, NA administration reversed the increase in ROS production and MDA levels induced by MPTP or MPP, as well as the decrease in SOD levels, suggesting the antioxidant properties of NA in PD. Meanwhile, we confirmed that NA can regulate oxidative stress and neuronal damage by activating the MEK/ERK pathway. Overall, we concluded that NA could alleviate MPTP-induced PD via MEK/ERK pathway.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*
  • Animals
  • Apoptosis* / drug effects
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • MAP Kinase Signaling System* / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress* / drug effects
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Reactive Oxygen Species
  • Neuroprotective Agents
  • Dopamine