Exposure to toxic occupations and their association with Parkinson’s disease: a systematic review with meta-analysis

Abstract

Objectives Earlier longitudinal reviews on environmental and occupational toxins and Parkinson’s disease (PD) risk have limitations. This study aimed to determine the strength of association between three types of toxic occupational exposures and the occurrence of PD by diagnostic methods. Methods A search was conducted of EMBASE, PubMed/Medline, Toxnet, LILACS, and Cochrane Library databases for longitudinal studies that assessed toxic occupational exposure, Parkinsonian, or related disorders, diagnosed by International Classification of Diseases (ICD) codes, medical records, or confirmation by a neurologist/nurse, and published in the English language from January 1990 to July 2021. Pooled risk ratios (RR) estimates were produced using random-effects models. Systematic review with meta-analysis synthesized the results. Study quality, heterogeneity, and publication bias were examined. High-quality articles that met the inclusion criteria were analyzed. Results Twenty-four articles were used in the analyses. The pooled RR for electromagnetic exposure and PD were (RR=1.03, 95% confidence interval [CI] 0.91–1.16) while the pooled RR between PD and metal and pesticide exposure were (RR=1.07, 95% CI 0.92–1.24) and (RR=1.41, 95% CI 1.20–1.65), respectively. Pooled RR for methods of diagnosis and their associations with PD were: confirmation by a neurologist or nurse (RR=2.17, 95% CI 1.32–3.54); ICD codes (RR=1.14, 95% CI 1.03–1.26), and medical records (RR=1.06, 95% CI 0.92–1.21). Conclusions Our systematic review provides robust evidence that toxic occupational exposures are significant risk factors for PD especially those diagnosed by neurologists or nurses using standardized methods.

New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders

“…In an in vitro experiment, siRNA to IL-37 (siIL-37) was transfected into human PBMCs stimulated by LPS. After IL-37 expression was specifically silenced, the production of IL-6 and other cytokines increased in a dose-dependent manner [82], indicating IL-37 can inhibit the inflammatory effect of IL-6 and play an anti-inflammatory role. Irene Tsilioni et al found that neuropeptide NT can stimulate human microglia to secrete IL-1β, CXCL8, and other cytokines that can be inhibited by IL-37 [91]; however, the specific mechanism underlying this inhibition remains unclear.…”

“…Exploring the roles of IL-37 in AD can be a promising direction for future research because caspase-1 is also an enzyme that cleaves the precursor of IL-37 and renders it active [31]. In addition, IL-37 has been shown to inhibit the inflammatory effects of other inflammatory cytokines, such as IL-6 and IL-1β in many other diseases [77][78][79][80][81][82]. In a temporomandibular joint study, IL-37 could convert M1 type macrophages to M2 type, thus alleviating inflammation [83].…”

“…For instance, given the differentially methylated promoter of the TNF-α gene in PD [23], the role of cigarette smoking in this relationship should be further explored. Additionally, smoking seems to affect histone acetylation and de-acetylation, and affect the expression of miRNAs in nonnerve tissues [82][83][84][85]. Thus, DNA methylation and possibly other epigenetic modifications might mediate the effects of smoking in PD.…”

Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson’s Disease Pathogenesis: A Narrative Review

“…For instance, given the differentially methylated promoter of the TNF- α gene in PD [ 23 ], the role of cigarette smoking in this relationship should be further explored. Additionally, smoking seems to affect histone acetylation and de-acetylation, and affect the expression of miRNAs in non-nerve tissues [ 82 , 83 , 84 , 85 ]. Thus, DNA methylation and possibly other epigenetic modifications might mediate the effects of smoking in PD.…”

Single cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease

“…However, environment clearly also makes an important contribution to PD. Epidemiological studies have shown that exposure to pesticides increases the risk of PD (Chambers-Richards et al, 2021; Fernagut et al, 2007; Hatcher et al, 2008). In particular, both the fungicide maneb (MN, manganese ethylene-bis-dithiocarbamate) and the herbicide paraquat (PQ) have been associated with PD (Ascherio et al, 2006; Wang et al, 2011).…”