Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9435104 | Progress in Neurobiology | 2005 | 24 Pages |
Abstract
Actual fields of research in neurobiology are not only aimed at understanding the different aspects of brain aging but also at developing strategies useful to preserve brain compensatory capacity and to prevent the onset of neurodegenerative diseases. Consistent with this trend much attention has been addressed to zinc metabolism. In fact, zinc acts as a neuromodulator at excitatory synapses and has a considerable role in the stress response and in the functionality of zinc-dependent enzymes contributing to maintaining brain compensatory capacity. In particular, the mechanisms that modulate the free zinc pool are pivotal for safeguarding brain health and performance. Alterations in zinc homeostasis have been reported in Parkinson's and Alzheimer's disease as well as in transient forebrain ischemia, seizures and traumatic brain injury, but little is known regarding aged brain. There is much evidence that that age-related changes, frequently associated to a decline in brain functions and impaired cognitive performances, could be related to dysfunctions affecting the intracellular zinc ion availability. A general agreement emerges from studies of humans' and rodents' old brains about an increased expression of metallothionein (MT) isoforms I and II, but dyshomogenous results are reported for MT-III, and it is still uncertain whether these proteins maintain in aging the protective role, as it occurs in adult/young age. At the same time, there is considerable evidence that amyloid-β deposition in Alzheimer's disease is induced by zinc, but the pathological significance and the causes of this phenomenon are still an open question. The scientific debate on the role of zinc and of some zinc-binding proteins in aging and neurodegenerative disorders, as well as on the beneficial effect of zinc supplementation in aged brain and neurodegeneration, is extensively discussed in this review.
Keywords
AP1CuZnSODMTF-1iNOSAMPANGFIP3GSSGGDHGADNMDAN-methyl-d-aspartateAβnNOScNOSZnTTNFPKCmGluRsLRP[Ca++]iMmpsPARP-1IL-1IL-6α2Minositol 1,4,5-trisphosphatel-HistidineNAD+NFκBROSSp1Adenosine TriphosphateATPAlpha2-macroglobulinAmyloid beta-peptideamyotrophic lateral sclerosisγ-aminobutyric acidinterleukin 1interleukin 6Alzheimer diseaseALSParkinson's diseaselong-term potentiationLTPsubstantia nigraHISCNSSynaptic zincinducible nitric oxide synthaseconstitutive nitric oxide synthaseDown's syndromecentral nervous systeminductively coupled plasma-mass spectrometryICP-MSnerve growth factortumor necrosis factornuclear factor κBMatrix metalloproteasesMetallothioneinscopper/zinc superoxide dismutaseSpecificity protein 1Neuronal NO synthaseNitric oxideNicotinamideactivator protein 1low density lipoprotein receptor-related proteinProtein kinase CPoly(ADP-ribose) polymerase-1KainateGABAglutathione disulphideglutamate dehydrogenaseGlutamate decarboxylaseReactive oxygen speciesIce
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Authors
Eugenio Mocchegiani, Carlo Bertoni-Freddari, Fiorella Marcellini, Marco Malavolta,