title: New therapeutic targets in Alzheimer's disease: brain deregulation of calcium and zinc.
abstract: The molecular determinants of Alzheimer's (AD) disease are still not completely known; however, in the past two decades, a large body of evidence has indicated that an important contributing factor for the disease is the development of an unbalanced homeostasis of two signaling cations: calcium (Ca(2+)) and zinc (Zn(2+)). Both ions serve a critical role in the physiological functioning of the central nervous system, but their brain deregulation promotes amyloid-β dysmetabolism as well as tau phosphorylation. AD is also characterized by an altered glutamatergic activation, and glutamate can promote both Ca(2+) and Zn(2+) dyshomeostasis. The two cations can operate synergistically to promote the generation of free radicals that further intracellular Ca(2+) and Zn(2+) rises and set the stage for a self-perpetuating harmful loop. These phenomena can be the initial steps in the pathogenic cascade leading to AD, therefore, therapeutic interventions aiming at preventing Ca(2+) and Zn(2+) dyshomeostasis may offer a great opportunity for disease-modifying strategies.
authors.affiliation: Molecular Neurology Unit, Center of Excellence on Aging (CeSI), Chieti, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Corona
authors.forename: A
authors.initials: A
authors.lastname: Pensalfini
authors.forename: V
authors.initials: V
authors.lastname: Frazzini
authors.forename: S L
authors.initials: SL
authors.lastname: Sensi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*; D015032:Zinc / Q000378:metabolism*
chemical_list: D015032:Zinc; D002118:Calcium