ArticleMetallomics : integrated biometal science2014
Manganese disturbs metal and protein homeostasis in Caenorhabditis elegans.
Article in Metallomics : integrated biometal science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Emergent latent neurotoxic effects of manganese following nominal chronic exposures in human stem cell and Caenorhabditis elegans models.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- The Role of Mitochondrial Quality Control in Manganese-induced Neurotoxicity.Neurotoxicity research · 2025Review
- Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders.Journal of xenobiotics · 2025Review
- Manganese Overexposure Alters Neurogranin Expression and Causes Behavioral Deficits in Larval Zebrafish.International journal of molecular sciences · 2024Article
- Arsenic Exposure Causes Global Changes in the Metalloproteome ofMicroorganisms · 2023Article
- Review
- BTBD9 attenuates manganese-induced oxidative stress and neurotoxicity by regulating insulin growth factor signaling pathway.Human molecular genetics · 2022Article
- Loss of slc39a14 causes simultaneous manganese hypersensitivity and deficiency in zebrafish.Disease models & mechanisms · 2022Article
- Multi-Elemental Analysis of Human Optic Chiasm-A New Perspective to Reveal the Pathomechanism of Nerve Fibers' Degeneration.International journal of environmental research and public health · 2022Article
- Article
- Evaluating the risk of manganese-induced neurotoxicity of parenteral nutrition: review of the current literature.Expert opinion on drug metabolism & toxicology · 2021Review
- Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis.Molecular nutrition & food research · 2021Article
- The Role of CaCells · 2020Review
- Iron and manganese-related CNS toxicity: mechanisms, diagnosis and treatment.Expert review of neurotherapeutics · 2019Review
- Article
- Application ofPreventive nutrition and food science · 2018Review
- The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions.Oxidative medicine and cellular longevity · 2018Review
- Manganese tissue accumulation and tyrosine hydroxylase immunostaining response in the Neotropical freshwater crab, Dilocarcinus pagei, exposed to manganese.Invertebrate neuroscience : IN · 2017Article
- Exposure, epidemiology, and mechanism of the environmental toxicant manganese.Environmental science and pollution research international · 2016Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Parkinson's disease (PD) is a debilitating motor and cognitive neurodegenerative disorder for which there is no cure. While aging is the major risk factor for developing PD, clear environmental risks have also been identified. Environmental exposure to the manganese (Mn) metal is a prominent risk factor for developing PD and occupational exposure to high levels of Mn can cause a syndrome known as manganism, which has symptoms that closely resemble PD. In this study, we developed a model of manganism in the environmentally tractable nematode, Caenorhabditis elegans. We find that, in addition to previously described modes of Mn toxicity, which primarily include mitochondrial dysfunction and oxidative stress, Mn exposure also significantly antagonizes protein homeostasis, another key pathological feature associated with PD and many age-related neurodegenerative diseases. Mn treatment activates the ER unfolded protein response, severely exacerbates toxicity in a disease model of protein misfolding, and alters aggregate solubility. Further, aged animals, which have previously been shown to exhibit decreased protein homeostasis, are particularly susceptible to Mn toxicity when compared to young animals, indicating that the aging process sensitizes animals to metal toxicity. Mn exposure also significantly alters iron (Fe) and calcium (Ca) homeostasis, which is important for mitochondrial and ER health and which may further compound toxicity. These findings indicate that modeling manganism in C. elegans can provide a useful platform for identifying therapeutic interventions for ER stress, proteotoxicity, and age-dependent susceptibilities, key pathological features of PD and other related neurodegenerative diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.