Towards improved screening of toxins for Parkinson's risk

Ling Shan; Harm J Heusinkveld; Kimberly C Paul; Samantha Hughes; Sirwan K L Darweesh; Bastiaan R Bloem; Judith R Homberg

doi:10.1038/s41531-023-00615-9

Towards improved screening of toxins for Parkinson's risk

NPJ Parkinsons Dis. 2023 Dec 19;9(1):169. doi: 10.1038/s41531-023-00615-9.

Authors

Ling Shan¹, Harm J Heusinkveld², Kimberly C Paul³, Samantha Hughes⁴, Sirwan K L Darweesh⁵, Bastiaan R Bloem⁵, Judith R Homberg⁶

Affiliations

¹ Department Neuropsychiatric Disorders, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands. l.shan@nin.knaw.nl.
² Centre for Health Protection, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands.
³ Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ A-LIFE Amsterdam Institute for Life and Environment, Section Environmental Health and Toxicology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
⁵ Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
⁶ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract

Parkinson's disease (PD) is a chronic, progressive and disabling neurodegenerative disorder. The prevalence of PD has risen considerably over the past decades. A growing body of evidence suggest that exposure to environmental toxins, including pesticides, solvents and heavy metals (collectively called toxins), is at least in part responsible for this rapid growth. It is worrying that the current screening procedures being applied internationally to test for possible neurotoxicity of specific compounds offer inadequate insights into the risk of developing PD in humans. Improved screening procedures are therefore urgently needed. Our review first substantiates current evidence on the relation between exposure to environmental toxins and the risk of developing PD. We subsequently propose to replace the current standard toxin screening by a well-controlled multi-tier toxin screening involving the following steps: in silico studies (tier 1) followed by in vitro tests (tier 2), aiming to prioritize agents with human relevant routes of exposure. More in depth studies can be undertaken in tier 3, with whole-organism (in)vertebrate models. Tier 4 has a dedicated focus on cell loss in the substantia nigra and on the presumed mechanisms of neurotoxicity in rodent models, which are required to confirm or refute the possible neurotoxicity of any individual compound. This improved screening procedure should not only evaluate new pesticides that seek access to the market, but also critically assess all pesticides that are being used today, acknowledging that none of these has ever been proven to be safe from a perspective of PD. Importantly, the improved screening procedures should not just assess the neurotoxic risk of isolated compounds, but should also specifically look at the cumulative risk conveyed by exposure to commonly used combinations of pesticides (cocktails). The worldwide implementation of such an improved screening procedure, would be an essential step for policy makers and governments to recognize PD-related environmental risk factors.

Publication types

Review