title: Significance of metallothioneins in aging brain.
abstract: Aging is an inevitable biological process, associated with gradual and spontaneous biochemical and physiological changes, and increased susceptibility to diseases. Chronic inflammation and oxidative stress are hallmarks of aging. Metallothioneins (MTs) are low molecular weight, zinc-binding, anti-inflammatory, and antioxidant proteins that provide neuroprotection in the aging brain through zinc-mediated transcriptional regulation of genes involved in cell growth, proliferation, and differentiation. In addition to Zn(2+) homeostasis, antioxidant role of MTs is routed through -SH moieties on cysteine residues. MTs are induced in aging brain as a defensive mechanism to attenuate oxidative and nitrative stress implicated in broadly classified neurodegenerative α-synucleinopathies. In addition, MTs as free radical scavengers inhibit Charnoly body (CB) formation to provide mitochondrial neuroprotection in the aging brain. In general, MT-1 and MT-2 induce cell growth and differentiation, whereas MT-3 is a growth inhibitory factor, which is reduced in Alzheimer's disease. MTs are down-regulated in homozygous weaver (wv/wv) mice exhibiting progressive neurodegeneration, early aging, morbidity, and mortality. These neurodegenerative changes are attenuated in MTs over-expressing wv/wv mice, suggesting the neuroprotective role of MTs in aging. This report provides recent knowledge regarding the therapeutic potential of MTs in neurodegenerative disorders of aging such as Parkinson's disease and Alzheimer's disease.
authors.affiliation: Saint James School of Medicine, Plaza Juliana 4, Kralendijk, The Dutch Caribbean, Bonaire, The Netherlands. Electronic address: Sharma@mail.sjsm.org.
authors.forename: Sushil
authors.initials: S
authors.lastname: Sharma
authors.affiliation: University of North Dakota School of Medicine, Department of Pharmacology, Physiology & Therapeutics, Grand Forks, ND, USA.
authors.forename: Manuchair
authors.initials: M
authors.lastname: Ebadi
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D000090023:Metallothionein 3; D008928:Mitochondria / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D008668:Metallothionein
keywords: Alzheimer’s disease; Charnoly body; Growth inhibitory factor; Metallothioneins; Neuroprotection; Oxidative stress; Parkinson’s disease; Reactive oxygen species