TY - JOUR
T1 - Brain manganese and the balance between essential roles and neurotoxicity
AU - Balachandran, Rekha C.
AU - Mukhopadhyay, Somshuvra
AU - McBride, Danielle
AU - Veevers, Jennifer
AU - Harrison, Fiona E.
AU - Aschner, Michael
AU - Haynes, Erin N.
AU - Bowman, Aaron B.
N1 - Publisher Copyright:
© 2020 Balachandran et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2020/5/8
Y1 - 2020/5/8
N2 - 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.
AB - 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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U2 - 10.1074/jbc.REV119.009453
DO - 10.1074/jbc.REV119.009453
M3 - Review article
C2 - 32188696
AN - SCOPUS:85084665518
SN - 0021-9258
VL - 295
SP - 6312
EP - 6329
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 19
ER -