Molecular aspects of metallothioneins in dementias

Gemma Comes, Anna Escrig, Yasmina Manso, Olaya Fernández-Gayol, Paula Sanchis, Amalia Molinero, Mercedes Giralt, Javier Carrasco, Juan Hidalgo

Research output: Chapter in BookChapterResearchpeer-review

Abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia, in which signs of neuroinflammation, oxidative stress, and neuronal death are important. Transition metals such as Zn, Fe, and Cu have also been shown to be altered in AD. The heavy metal-binding proteins, metallothioneins (MTs), have been shown to be influenced by AD and to have significant antioxidant, antiinflammatory, and antiapoptotic properties. A number of mouse models of AD have been created, and in some of them, such as the Tg2576 mice, the regulation of the MT family of proteins has been studied. The MT1+2 isoforms are typically upregulated by AD-like pathology, whereas the results for MT3 are less clear-cut. MTs had different effects on survival, depending on the isoform and the sex and age of the mouse (perinatal/weaning or later). MTs in general promote the formation of amyloid plaques (dense core and diffuse) in the hippocampus and, to a lesser extent, in the cortex, particularly in females. MT1+2 had an inhibitory effect on glial cells in young but not old mice, in which amyloid-β plaques are prominent. The absence of MT3 decreased the CA1 hippocampal layer, suggesting an important role in neuronal survival.

Original languageEnglish
Title of host publicationGenetics, Neurology, Behavior, and Diet in Dementia
Subtitle of host publicationThe Neuroscience of Dementia, Volume 2
PublisherElsevier
Pages115-130
Number of pages16
ISBN (Electronic)9780128158685
DOIs
Publication statusPublished - 1 Jan 2020

Keywords

  • Alzheimer’s disease
  • Amyloid plaques
  • Gliosis
  • Metallothionein
  • Neuroinflammation
  • Neuronal loss
  • Tg2576

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