Exposing the role of metals in neurological disorders: a focus on manganese. Issue 7 (July 2022)

• Record Type: Journal Article
• Authors: Kim, Hyunjin; Harrison, Fiona E.; Aschner, Michael; Bowman, Aaron B.
• Is Part Of: Trends in molecular medicine. Volume 28:Issue 7(2022)
• Page Start: 555
• Page End: 568
• Publication Date: 2022-07
• Subjects: acute exposures -- chronic exposures -- manganese -- metals -- neurodegeneration -- neurodevelopmental; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2022.04.011
• Languages: English
• ISSNs: 1471-4914

Abstract

Abstract : Metals are ubiquitous chemical entities involved in a myriad of biological processes. Despite their integral role in sustaining life, overexposure can lead to deleterious neurological outcomes posing a public health concern. Excess exposure to metals has been associated with aberrant neurodevelopmental and neurodegenerative diseases and prominently contributes to environmental risk for neurological disorders. Here, we use manganese (Mn) to exemplify the gap in our understanding of the mechanisms behind acute metal toxicity and their relationship to chronic toxicity and disease. This challenge frustrates understanding of how individual exposure histories translate into preventing and treating brain diseases from childhood through old age. We discuss ways to enhance the predictive value of preclinical models and define mechanisms of chronic, persistent, and latent neurotoxicity. Highlights: Metals, though some are also essential for life, are ubiquitous environmental as well as occupational neurotoxicants implicated in brain disorders. Manganese (Mn) is also an essential micronutrient required for central nervous system (CNS) health, but overexposure can cause neurological symptoms including cognitive, behavioral, and motor deficits. Perturbations in brain Mn homeostasis are implicated in a myriad of neurological diseases. Mn toxicity can manifest as neurodegenerative or neurodevelopmental disorders with variable latency across a person's lifetime and may persist even after cessation of exposure. An individual's response to Mn exposure is the result of an elaborate crosstalk between biological factors and exposure properties at the gene–environment interphase. Majority of mechanistic studies have been centered on acute toxicity, but mechanisms underlying chronic exposure and its relevance to human health is less understood. Detailed understanding of mechanisms of chronic metal toxicity is imperative for assessing the risks associated with each metal exposure in developing neurological disorders.