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.