Brain manganese and the balance between essential roles and neurotoxicity

Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterat...

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Published inThe Journal of biological chemistry Vol. 295; no. 19; pp. 6312 - 6329
Main Authors Balachandran, Rekha C., Mukhopadhyay, Somshuvra, McBride, Danielle, Veevers, Jennifer, Harrison, Fiona E., Aschner, Michael, Haynes, Erin N., Bowman, Aaron B.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 08.05.2020
American Society for Biochemistry and Molecular Biology
Subjects
Animals
brain
Brain - metabolism
Brain - pathology
Cognition
Homeostasis
Humans
JBC Reviews
manganese
Manganese - metabolism
Manganese - toxicity
metal
metal homeostasis
neurodegeneration
neurodegenerative disease
neurodevelopment
Neurons - metabolism
Neurons - pathology
Neurotoxicity Syndromes - metabolism
neurotoxin
neurotransmitter
toxicology
toxicology
homeostasis
neurodegenerative disease
neurodevelopment
metal
neurodegeneration
neurotoxin
metal homeostasis
brain
neurotransmitter
manganese
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Summary:Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity.
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These authors contributed equally to this work.
Edited by Paul E. Fraser
ISSN:0021-9258
1083-351X
1083-351X
DOI:10.1074/jbc.REV119.009453