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Rosmarinic Acid Inhibits Mitochondrial Damage by Alleviating Unfolded Protein Response

Guoen Cai1, Fabin Lin1,2, Dihang Wu1,2

  • 1Department of Neurology, Fujian Medical University Union Hospital, Fujian Key Laboratory of Molecular Neurology, Institute of Clinical Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, China.

Frontiers in Pharmacology
|June 2, 2022
PubMed

Insights

Rosmarinic acid (RA) protects against Parkinson's disease by preventing mitochondrial damage. RA alleviates the mitochondrial unfolded protein response (mtUPR), safeguarding dopaminergic neurons from MPTP-induced injury.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Mitochondria are crucial for cellular functions, and their dysfunction is linked to Parkinson's disease (PD) via the mitochondrial unfolded protein response (mtUPR).
  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin used to model PD, causing mitochondrial damage in dopaminergic neurons.

Purpose of the Study:

  • To investigate the protective effects of Rosmarinic acid (RA) against MPTP-induced mitochondrial damage in Parkinson's disease.
  • To elucidate the underlying mechanism involving the mitochondrial unfolded protein response (mtUPR).

Main Methods:

  • MPTP mouse model of Parkinson's disease and SH-SY5Y neuroblastoma cells were used.
  • Mice and cells were pretreated with Rosmarinic acid (RA) before MPTP exposure.
  • Evaluated motor function, dopaminergic neuronal survival, cell viability, oxidative stress, and expression of key mtUPR-related genes (HSPA9, HSPE1, CLPP, LONP1, SIRT4).

Main Results:

  • RA pretreatment significantly reduced motor impairments and dopaminergic neuronal loss in MPTP-injected mice.
  • RA protected SH-SY5Y cells from MPTP-induced loss of viability, morphological damage, and oxidative stress.
  • RA suppressed MPTP-induced mtUPR and downregulated the expression of HSPA9, HSPE1, CLPP, LONP1, and SIRT4, preventing mitochondrial dysfunction.

Conclusions:

  • Rosmarinic acid demonstrates significant neuroprotective effects against MPTP-induced Parkinson's disease pathology.
  • RA alleviates mitochondrial damage by inhibiting the mitochondrial unfolded protein response (mtUPR).
  • These findings suggest RA as a potential therapeutic agent for Parkinson's disease by targeting mitochondrial dysfunction.
Keywords:
immunlogymitochondrial damagemtUPRrosmarinic acidsubstantia nigra

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