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Microbiota and Other Preventive Strategies and Non-genetic Risk Factors in Parkinson's Disease.

ABSTRACT: The exact cause of Parkinson's disease (PD), the second most prevalent neurodegenerative disease in modern societies, is still unknown. Many scientists point out that PD is caused by a complex interaction between different factors. Although the main risk factor is age, there are other influences, genetic and environmental, that individually or in combination may trigger neurodegenerative changes leading to PD. Nowadays, research remains focused on better understanding which environmental factors are related to the risk of developing PD and why. In line with the knowledge on evidence on exposures that prevent/delay PD onset or that impact on disease progression, the aims of this review were: (i) to comment on the non-genetic risk factors that mainly affect idiopathic PD; and (ii) to comment on seemingly reliable preventive interventions. We discuss both environmental factors that may affect the central nervous system (CNS) or the intestinal tract, and the likely mechanisms underlying noxious or protective actions. Knowledge on risk, protective factors, and mechanisms may help to envisage why nigral dopaminergic neurons are so vulnerable in PD and, eventually, to design new strategies for PD prevention and/or anti-PD therapy. This article reviews the variety of the known and suspected environmental factors, such as lifestyle, gut microbiota or pesticide exposition, and distinguishes between those that are harmful or beneficial for the PD acquisition or progression. In fact, the review covers one of the most novel players in the whole picture, and we address the role of microbiota on keeping a healthy CNS and/or on preventing the "side-effects" related to aging.

SUBMITTER: Franco R

PROVIDER: S-EPMC7080700 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Microbiota and Other Preventive Strategies and Non-genetic Risk Factors in Parkinson's Disease.

Franco Rafael R Rivas-Santisteban Rafael R Reyes-Resina Irene I Navarro Gemma G Martínez-Pinilla Eva E

Frontiers in aging neuroscience 20200312

The exact cause of Parkinson's disease (PD), the second most prevalent neurodegenerative disease in modern societies, is still unknown. Many scientists point out that PD is caused by a complex interaction between different factors. Although the main risk factor is age, there are other influences, genetic and environmental, that individually or in combination may trigger neurodegenerative changes leading to PD. Nowadays, research remains focused on better understanding which environmental factors ...[more]

PMID: 32226375

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Project description:BackgroundEpidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties.ObjectiveWe used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors.MethodsWe used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses.ResultsWe confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31).ConclusionsWe show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Dataset Information

Microbiota and Other Preventive Strategies and Non-genetic Risk Factors in Parkinson's Disease.

Publications

Microbiota and Other Preventive Strategies and Non-genetic Risk Factors in Parkinson's Disease.

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