Title:Oxidative Stress, Pro-Inflammatory Cytokines, and Antioxidants Regulate Expression Levels of MicroRNAs in Parkinson’s Disease
Volume: 10
Issue: 3
Author(s): Kedar N. Prasad*
Affiliation:
- Engage Global, 245 El-Faisan Drive, San Rafael, CA 94903,United States
Keywords:
Alpha-synuclein, antioxidants, chronic inflammation, microRNAs, neurodegeneration, oxidative stress.
Abstract: Background: Parkinson’s disease (PD) is a slow progressive neurodegenerative disease
associated with abnormal function of extrapyramidal system. Although several biochemical and
genetic defects are identified, increased oxidative stress and chronic inflammation are one of the
earliest events that initiate and promote PD. Oxidative stress also participates in impaired nonmotor
symptoms. The levels of microRNAs that are evolutionarily conserved single-stranded noncoding
RNAs of approximately 22 nucleotide in length may have a role in PD.
Method: Published studies on changes in the levels of microRNAs in PD were critically reviewed,
and the role of Reactive Oxygen Species (ROS), pro-inflammatory cytokines, and antioxidants in
regulating the levels of microRNAs was evaluated.
Results: MicroRNAs levels were altered in PD. Downregulated microRNAs cause neurodegeneration
by decreasing the levels of Nrf2 (nuclear transcriptional factor-2), mTOR (mammalian target
of rapamycin), and DJ-1 and Parkin genes; and by increasing the levels of alpha-synuclein, RelA,
Bim and Calpain-1, and A2AR (adenosine A2A receptor). Upregulated microRNAs cause degeneration
of nerve cells by decreasing the levels of IGF-1 (Insulin Growth Factor-1), GRP78 (glucose
regulated protein 78), DJ-1, and Hsc-70 (Heat- Shock Protein-70) that enhanced alpha-synuclein
levels. ROS and pro-inflammatory cytokines cause neurodegeneration by altering the levels of microRNAs.
Antioxidants that protect neurons by reducing oxidative stress and chronic inflammation
altered the levels of microRNAs.
Conclusion: Increased oxidative stress and chronic inflammation may cause neurodegeneration in
PD by altering the levels of microRNAs and their target proteins. Antioxidants may provide neuroprotection
by changing the levels of microRNAs and their target proteins.
