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

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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