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Oxidative Stress, Pro-Inflammatory Cytokines, and Antioxidants Regulate Expression Levels of MicroRNAs in Parkinson’s Disease

[ Vol. 10 , Issue. 3 ]

Author(s):

Kedar N. Prasad   Pages 177 - 184 ( 8 )

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.

Keywords:

Alpha-synuclein, antioxidants, chronic inflammation, microRNAs, neurodegeneration, oxidative stress.

Affiliation:

Engage Global, 245 El-Faisan Drive, San Rafael, CA 94903

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