Altered manganese homeostasis

Implications for BLI-3-dependent dopaminergic neurodegeneration and SKN-1 protection in C. elegans

Sudipta Chakraborty, Michael Aschner

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The role of environmental factors in the etiology of neurodegenerative disorders, such as in Parkinson's disease (PD), has become increasingly imperative for examination, as genetics can only partially account for most cases. The heavy metal manganese (Mn) falls into this category of environmental contributors, as it is both essential but also neurotoxic upon overexposure and produces Parkinsonian symptomatology. In order to understand its toxicity, this review focuses on the various aspects of improper Mn homeostasis and its consequences using the genetically amenable Caenorhabditis elegans model. Namely, the roles of Mn transporter homologs for the divalent metal transporter 1 (DMT1) will be discussed, as Mn homeostasis is initially governed by proper cellular transport. Mn dyshomeostasis can result in enhanced oxidative stress through synergistic actions of dopamine oxidation that is dependent on the C. elegans dual oxidase BLI-3. Finally, neuroprotection conferred by the antioxidant transcription factor Nrf2 (C. elegans SKN-1) may signify a potential therapeutic approach against Mn toxicity.

Original languageEnglish (US)
Pages (from-to)183-187
Number of pages5
JournalJournal of Trace Elements in Medicine and Biology
Volume26
Issue number2-3
DOIs
StatePublished - Jun 2012
Externally publishedYes

Fingerprint

Manganese
Homeostasis
Caenorhabditis elegans
Toxicity
Oxidative stress
Heavy Metals
Neurodegenerative Diseases
Parkinson Disease
Dopamine
Oxidoreductases
Oxidative Stress
Transcription Factors
Antioxidants
Oxidation

Keywords

  • BLI-3
  • DMT1/SMF
  • Manganese
  • Parkinson's disease
  • SKN-1/Nrf2

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry
  • Molecular Medicine

Cite this

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