Zinc dyshomeostasis: A key modulator of neuronal injury

Margherita Capasso, Jade Ming Jeng, Marco Malavolta, Eugenio Mocchegiani, Stefano L. Sensi

Research output: Contribution to journalArticlepeer-review


Zn2+ is a potently toxic cation involved in the neuronal injury observed in cerebral ischemia, epilepsy, and brain trauma. Toxic Zn2+ accumulation may result from either trans-synaptic Zn2+ movement and/or cation mobilization from intracellular sites. To gain entry to the cytosol, Zn2+ can flux through glutamate receptor-associated channels, voltage-sensitive calcium channels, or Zn2+-sensitive membrane transporters, while metallothioneins and mitochondria provide sites of intracellular Zn2+ release. Intracellular Zn2+ homeostasis is sensitive to patho-physiological environmental changes, such as acidosis, inflammation and oxidative stress. The mechanisms by which Zn2+ exerts its neurotoxicity include mitochondrial and extra-mitochondrial production of reactive oxygen species and disruption of metabolic enzymatic activity, ultimately leading to activation of apoptotic and/or necrotic processes. Beside acute neuronal injury, an exciting new area of investigation is offered by the role of Zn2+ dysmetabolism in Alzheimer's disease as the cation acts as a potent trigger for Aβ aggregation and plaque formation. Finally, recent findings suggest that alteration of Zn2+ homeostasis might also be a critical contributor to aging-related neurodegenerative processes. Thus, multiple evidence suggest that modulation of intracellular and extracellular Zn2+ might be an important therapeutical target for the treatment of a vast array of neurological conditions ranging from stroke to Alzheimer's disease.

Original languageEnglish
Pages (from-to)93-108
Number of pages16
JournalJournal of Alzheimer's Disease
Issue number2
Publication statusPublished - 2005


  • Alzheimer's disease
  • Brain aging
  • Brain trauma
  • Epilepsy
  • Ischemia
  • Oxidative stress
  • Zn dyshomeostasis

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology


Dive into the research topics of 'Zinc dyshomeostasis: A key modulator of neuronal injury'. Together they form a unique fingerprint.

Cite this