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Mechanism of Gene-Environment Interactions Driving Glial Activation in Parkinson’s Diseases

  • Mechanisms of Toxicity (JR Richardson, Section Editor)
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Abstract

Purpose of Review

Parkinson’s disease (PD) is the most prevalent motor disorder and is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the brain. Though the pathology of PD is well established, the cause of this neuronal loss is not well understood. Approximately 90% of PD cases are sporadic, and the environment plays a significant role in disease pathogenesis. The etiology of PD is highly complex, with neuroinflammation being one of the most critical factors implicated in PD. However, the signaling mechanisms underlying neuroinflammation and its interaction with environmental factors are unclear.

Recent Findings

Astroglia and microglia are the two principal cells that play an essential role in maintaining neuronal health in many ways, including through immunological means. Exposure to environmental stressors from various sources affects these glial cells leading to chronic and sustained inflammation. Recent epidemiological studies have identified an interaction among environmental factors and glial genes in Parkinson’s disease. Mechanistic studies have shown that exposure to pesticides like rotenone and paraquat, neurotoxic metals like manganese and lead, and even diesel exhaust fumes induce glial activation by regulating various key inflammatory pathways, including the inflammasomes, NOX pathways, and others.

Summary

This review aims to discuss the recent advances in understanding the mechanism of glial induction in response to environmental stressors and discuss the potential role of gene-environment interaction in driving glial activation.

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Funding

This work was supported by a grant from Brigham and Women’s Hospital and the Colgate-Palmolive Postdoctoral Fellowship Award in In Vitro Toxicology (SS).

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  1. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA

    Souvarish Sarkar

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This article is part of the Topical Collection on Mechanisms of Toxicity

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Sarkar, S. Mechanism of Gene-Environment Interactions Driving Glial Activation in Parkinson’s Diseases. Curr Envir Health Rpt 8, 203–211 (2021). https://doi.org/10.1007/s40572-021-00320-w

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