Activation of Lrrk2 and α-Synuclein in substantia nigra, striatum, and cerebellum after chronic exposure to arsenite

Drobná, Zuzana

doi:10.1016/j.taap.2020.115278

Cited by 3 publications

(1 citation statement)

References 51 publications

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“…Studies in neuroblastoma cell lines, rats, and mice revealed a time-dependent accumulation and oligomerization/aggregation of αSyn during exposure to low As(III) concentrations (0.03–0.3 µM) [ 274 , 275 ]. Chronic exposure of mice to environmental relevant (0.65–6.5 μM) and high (65 μM) concentrations of As(III) in drinking water caused a dose-dependent increase in the phosphorylation of leucine-rich repeat kinase 2 (LRRK2) and αSyn in different brain regions [ 276 ]. Both LRRK2 and αSyn phosphorylation are implicated in PD, and phosphorylation is known to modulate αSyn oligomerization and fibrilization, as well as the formation of Lewy bodies and neurotoxicity [ 277 , 278 ].…”

Section: Metalloid-induced Genotoxicity and Proteotoxicity: A Double-...mentioning

confidence: 99%

Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony

Wysocki,

Rodrigues,

Litwin

et al. 2023

Cell. Mol. Life Sci.

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Arsenic and antimony are metalloids with profound effects on biological systems and human health. Both elements are toxic to cells and organisms, and exposure is associated with several pathological conditions including cancer and neurodegenerative disorders. At the same time, arsenic- and antimony-containing compounds are used in the treatment of multiple diseases. Although these metalloids can both cause and cure disease, their modes of molecular action are incompletely understood. The past decades have seen major advances in our understanding of arsenic and antimony toxicity, emphasizing genotoxicity and proteotoxicity as key contributors to pathogenesis. In this review, we highlight mechanisms by which arsenic and antimony cause toxicity, focusing on their genotoxic and proteotoxic effects. The mechanisms used by cells to maintain proteostasis during metalloid exposure are also described. Furthermore, we address how metalloid-induced proteotoxicity may promote neurodegenerative disease and how genotoxicity and proteotoxicity may be interrelated and together contribute to proteinopathies. A deeper understanding of cellular toxicity and response mechanisms and their links to pathogenesis may promote the development of strategies for both disease prevention and treatment.

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