Physiological Roles of Metallothioneins in Central Nervous System Diseases

Biol Pharm Bull. 2018;41(7):1006-1013. doi: 10.1248/bpb.b17-00856.


Metallothioneins (MTs) are small-molecular weight metal-binding proteins involved in the maintenance of tissue structure, efficient metal metabolism, and metal detoxification and have an antioxidative effect. Moreover, MTs are expressed as four isoforms, and there are no known patterns in their localization with various effects. According to recent studies, MTs affect central nervous system (CNS) diseases, and many reports suggest that each isoform of MT has a protective effect against disease. Notably, MTs are involved in regions of diseases related to unmet medical needs, and MTs affect intractable neurological diseases, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). This review specifically focuses on MT-related ocular diseases, cerebral ischemia, psychological disorders, ALS, and SMA. Each of these diseases has a separate cause, but the conditions are related to MTs. To understand the physiological roles of MTs in CNS diseases, we reviewed the current literature on the complex interactions between each MT, pathological conditions, and perspectives. We also discuss current evidence on the expression and function of MTs for diagnosis and new therapeutic strategies.

Keywords: metallothionein (MT); neovascularization; neurodegeneration.

Publication types

  • Review

MeSH terms

  • Central Nervous System Diseases / diagnosis
  • Central Nervous System Diseases / drug therapy
  • Central Nervous System Diseases / pathology*
  • Eye Diseases / diagnosis
  • Eye Diseases / drug therapy
  • Eye Diseases / pathology*
  • Humans
  • Metallothionein / metabolism*
  • Molecular Targeted Therapy / methods
  • Protein Isoforms / metabolism


  • Protein Isoforms
  • Metallothionein