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Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025Lead, a toxic heavy metal, is prevalent in various industrial applications, contributing to environmental contamination and significant health concerns. Lead affects various body systems, especially the brain, causing long-lasting cognitive and behavioral changes. While most studies have focused on continuous lead exposure, intermittent exposure, such as that caused by migration or relocations, has received less attention. Importantly, lead exposure intensifies the severity of Parkinson's disease (PD) and dementia with Lewy bodies, diseases involving the accumulation of alpha-synuclein (aSyn) in the brain and in the gut. Although the precise mechanisms underlying these observations remain unclear, oxidative stress and mitochondrial dysfunction likely play a role. Here, we investigated how two different profiles of lead exposure - continuous and intermittent - affect models of synucleinopathies. We found that lead exposure enhances the formation of aSyn inclusions, resulting in an increase in both their number and size in cell models. In addition, we found that animals injected with aSyn pre-formed fibrils display serine 129-phosphorylated aSyn inclusions and a reduction in astrocytes in the substantia nigra. These animals also display neuronal damage and alterations in locomotor activity, exploration behavior, anxiety, memory impairments and hypertension. Our results suggest a mechanistic link between environmental lead exposure and the onset and progression of diseases associated with aSyn pathology. Understanding the molecular and cellular interactions between lead and aSyn is crucial for shaping public health policies and may provide novel insight into strategies for mitigating the impact of environmental toxins on neurodegenerative processes involved in Parkinson's disease and related synucleinopathies.
Author(s): Shvachiy L, Amaro-Leal A, Machado F, Rocha I, Geraldes V, Outeiro TF
Publication type: Article
Publication status: Published
Journal: Chemosphere
Year: 2025
Volume: 380
Print publication date: 01/06/2025
Online publication date: 09/05/2025
Acceptance date: 05/05/2025
Date deposited: 20/05/2025
ISSN (print): 0045-6535
ISSN (electronic): 1879-1298
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.chemosphere.2025.144477
DOI: 10.1016/j.chemosphere.2025.144477
Data Access Statement: The data presented in this study are available on request from the corresponding authors upon reasonable requests.
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