The epigenetic mechanisms involved in mitochondrial dysfunction: Implication for Parkinson’s disease

Zixuan Chen*, Madiha Rasheed, Yulin Deng*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

21 Citations (Scopus)

Abstract

Mitochondrial dysfunction is one of the crucial factors involved in PD’s pathogenicity, which emerges from a combination of genetic and environmental factors. These factors cause differential molecular expression in neurons, such as varied transcriptional regulation of genes, elevated oxidative stress, α-synuclein aggregation and endogenous neurotoxins release, which induces epigenetic modifications and triggers energy crisis by damaging mitochondria of the dopaminergic neurons (DN). So far, these events establish a complicated relationship with underlying mechanisms of mitochondrial anomalies in PD, which has remained unclear for years and made PD diagnosis and treatment extremely difficult. Therefore, in this review, we endeavored to discuss the complex association of epigenetic modifications and other associated vital factors in mitochondrial dysfunction. We propose a hypothesis that describes a vicious cycle in which mitochondrial dysfunction and oxidative stress act as a hub for regulating DA neuron's fate in PD. Oxidative stress triggers the release of endogenous neurotoxins (CTIQs) that lead to mitochondrial dysfunction along with abnormal α-synuclein aggregation and epigenetic modifications. These disturbances further intensify oxidative stress and mitochondrial damage, amplifying the synthesis of CTIQs and works vice versa. This vicious cycle may result in the degeneration of DN to hallmark Parkinsonism. Furthermore, we have also highlighted various endogenous compounds and epigenetic marks (neurotoxic and neuroprotective), which may help for devising future diagnostic biomarkers and target specific drugs using novel PD management strategies.

Original languageEnglish
Article numbere13012
JournalBrain Pathology
Volume32
Issue number3
DOIs
Publication statusPublished - May 2022

Keywords

  • Parkinson's disease
  • endogenous neurotoxins
  • epigenetics
  • mitochondrial dysfunction
  • neurodegenerative
  • oxidative stress
  • α-synuclein

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Chen, Z., Rasheed, M., & Deng, Y. (2022). The epigenetic mechanisms involved in mitochondrial dysfunction: Implication for Parkinson’s disease. Brain Pathology, 32(3), Article e13012. https://doi.org/10.1111/bpa.13012