Manganese-induced neurodegenerative diseases and possible therapeutic approaches

Airton C. Martins, Priscila Gubert, Gustavo R. Villas Boas, Marina Meirelles Paes, Abel Santamaría, Eunsook Lee, Alexey A. Tinkov, Aaron B. Bowman, Michael Aschner

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations

Abstract

Introduction: Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and prion disease represent important public health concerns. Exposure to high levels of  heavy metals such as manganese (Mn) may contribute to their development. Areas covered: In this critical review, we address the role of Mn in the etiology of neurodegenerative diseases and discuss emerging treatments of Mn overload, such as chelation therapy. In addition, we discuss natural and synthetic compounds under development as prospective therapeutics. Moreover, bioinformatic approaches to identify new potential targets and therapeutic substances to reverse the neurodegenerative diseases are discussed. Expert opinion: Here, the authors highlight the importance of better understanding the molecular mechanisms of toxicity associated with neurodegenerative diseases, and the role of Mn in these diseases. Additional emphasis should be directed to the discovery of new agents to treat Mn-induced diseases, since present day chelator therapies have limited bioavailability. Furthermore, the authors encourage the scientific community to develop research using libraries of compounds to screen those compounds that show efficacy in regulating brain Mn levels. In addition, bioinformatics may provide novel insight for pathways and clinical treatments associated with Mn-induced neurodegeneration, leading to a new direction in Mn toxicological research.

Original languageEnglish (US)
Pages (from-to)1109-1121
Number of pages13
JournalExpert review of neurotherapeutics
Volume20
Issue number11
DOIs
StatePublished - Nov 2020

Keywords

  • Alzheimer’s disease
  • Huntington’s disease
  • Parkinson’s disease
  • amyotrophic lateral sclerosis
  • heavy metals
  • manganese

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology
  • Pharmacology (medical)

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