Brain manganese and the balance between essential roles and neurotoxicity

Rekha C. Balachandran, Somshuvra Mukhopadhyay, Danielle McBride, Jennifer Veevers, Fiona E. Harrison, Michael Aschner, Erin N. Haynes, Aaron B. Bowman

Research output: Contribution to journalReview articlepeer-review

131 Scopus citations


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.

Original languageEnglish
Pages (from-to)6312-6329
Number of pages18
JournalJournal of Biological Chemistry
Issue number19
StatePublished - May 8 2020

Bibliographical note

Funding Information:
This work was supported by NIEHS, National Institutes of Health, Grants R01 ES024812 (to S. M.), RO1 ES016931 (to A. B. B.), RO1 ES010563 (to A. B. B. and M. A.), R01 ES031401 (to F. E. H. and A. B. B.), and R01 ES026446 (to E. N. H.) and by Veterans Affairs Grant I01 CX001610-01 (to F. E. H.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2020 Balachandran et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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