Metallothionein-I+II in neuroprotection

Biofactors. 2009 Jul-Aug;35(4):315-25. doi: 10.1002/biof.44.


Metallothionein (MT)-I+II synthesis is induced in the central nervous system (CNS) in response to practically any pathogen or disorder, where it is increased mainly in reactive glia. MT-I+II are involved in host defence reactions and neuroprotection during neuropathological conditions, in which MT-I+II decrease inflammation and secondary tissue damage (oxidative stress, neurodegeneration, and apoptosis) and promote post-injury repair and regeneration (angiogenesis, neurogenesis, neuronal sprouting and tissue remodelling). Intracellularly the molecular MT-I+II actions involve metal ion control and scavenging of reactive oxygen species (ROS) leading to cellular redox control. By regulating metal ions, MT-I+II can control metal-containing transcription factors, zinc-finger proteins and p53. However, the neuroprotective functions of MT-I+II also involve an extracellular component. MT-I+II protects the neurons by signal transduction through the low-density lipoprotein family of receptors on the cell surface involving lipoprotein receptor-1 (LRP1) and megalin (LRP2). In this review we discuss the newest data on cerebral MT-I+II functions following brain injury and experimental autoimmune encephalomyelitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain Injuries / physiopathology
  • Encephalitis / prevention & control
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Erythropoietin / physiology
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-2 / physiology
  • Metallothionein / biosynthesis
  • Metallothionein / physiology*
  • Multiple Sclerosis / physiopathology
  • Neurodegenerative Diseases / drug therapy
  • Neuroprotective Agents*
  • Oxidative Stress / drug effects
  • Receptors, Cell Surface / physiology
  • Signal Transduction


  • Low Density Lipoprotein Receptor-Related Protein-2
  • Neuroprotective Agents
  • Receptors, Cell Surface
  • metallothionein receptor
  • Erythropoietin
  • Metallothionein