Significance of metallothioneins in aging brain

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• 作者：Sushil Sharma ; Manuchair Ebadi
• 关键词：AD ; Alzheimer&rsquo ; s disease ; GFP ; green-fluorescence protein ; H2O2 ; hydrogen peroxide ; 6-OH-DA ; 6-hydroxy dopamine ; MT ; metallothionien ; MTdko ; metallothionein double knock out ; MTtrans ; metallothionein transgenic ; 伪-Syn-MTtkoMice ; 伪-synuclein-MTs triple knockout mice ; wv/wv-MTs Mice ; MTs over-expressing weaver mice ; MicroPET ; micro-positron emission tomography ; RhOmgko ; mitochondrial genome knock out ; SIN-1 ; 3-morpholinosydnonimine ; MPTP ; 1 ; methyl 4-phenyl ; 1 ; 2 ; 3 ; 6 ; tetrahydropyridine ; MPP
• 刊名：Neurochemistry International
• 出版年：January, 2014
• 年：2014
• 卷：65
• 期：Complete
• 页码：40-48
• 全文大小：413 K

文摘

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 Zn²⁺ 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 伪-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鈥檚 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鈥檚 disease and Alzheimer鈥檚 disease.