Roles of the metallothionein family of proteins in the central nervous system

Juan Hidalgo, Michael Aschner, Paolo Zatta, Milan Vašák

Research output: Contribution to journalArticlepeer-review

370 Scopus citations


Metallothioneins (MTs) constitute a family of proteins characterized by a high heavy metal [Zn(II), Cu(I)] content and also by an unusual cysteine abundance. Mammalian MTs are comprised of four major isoforms designated MT-1 through MT-4. MT-1 and MT-2 are expressed in most tissues including the brain, whereas MT-3 (also called growth inhibitory factor) and MT-4 are expressed predominantly in the central nervous system and in keratinizing epithelia, respectively. All MT isoforms have been implicated in disparate physiological functions, such as zinc and copper metabolism, protection against reactive oxygen species, or adaptation to stress. In the case of MT-3, an additional involvement of this isoform in neuromodulatory events and in the pathogenesis of Alzheimer's disease has also been suggested. It is essential to gain insight into how MTs are regulated in the brain in order to characterize MT functions, both in normal brain physiology, as well as in pathophysiological states. The focus of this review concerns the biology of the MT family in the context of their expression and functional roles in the central nervous system.

Original languageEnglish (US)
Pages (from-to)133-145
Number of pages13
JournalBrain Research Bulletin
Issue number2
StatePublished - May 15 2001
Externally publishedYes


  • Copper
  • Metal-thiolate complexes
  • Neurodegenerative diseases
  • Oxidative stress
  • Zinc

ASJC Scopus subject areas

  • Neuroscience(all)


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