Administration of quercetin improves mitochondria quality control and protects the neurons in 6-OHDA-lesioned Parkinson's disease models

Aging (Albany NY). 2021 Apr 20;13(8):11738-11751. doi: 10.18632/aging.202868. Epub 2021 Apr 20.

Abstract

Mounting evidence suggests that mitochondrial dysfunction and impaired mitophagy lead to Parkinson's disease (PD). Quercetin, one of the most abundant polyphenolic flavonoids, displays many health-promoting biological effects in many diseases. We explored the neuroprotective effect of quercetin in vivo in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD and in vitro in 6-OHDA-treated PC12 cells. In vitro, we found that quercetin (20 μM) treatment improved mitochondrial quality control, reduced oxidative stress, increased the levels of the mitophagy markers PINK1 and Parkin and decreased α-synuclein protein expression in 6-OHDA-treated PC12 cells. Moreover, our in vivo findings demonstrated that administration of quercetin also relieved 6-OHDA-induced progressive PD-like motor behaviors, mitigated neuronal death and reduced mitochondrial damage and α-synuclein accumulation in PD rats. Furthermore, the neuroprotective effect of quercetin was suppressed by knockdown of either Pink1 or Parkin.

Keywords: Parkinson's disease; mitochondria quality control; mitophagy; quercetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitophagy / drug effects*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage*
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Oxidopamine / administration & dosage
  • Oxidopamine / toxicity
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / drug therapy*
  • Parkinson Disease, Secondary / pathology
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Quercetin / administration & dosage*
  • Rats
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • alpha-Synuclein / metabolism

Substances

  • Neuroprotective Agents
  • Snca protein, rat
  • alpha-Synuclein
  • Oxidopamine
  • Quercetin
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • PTEN-induced putative kinase