Brain, metalloproteins

Within seconds of an ischemic insult, normal brain electrical activity ceases, as a result of the activation of membrane K+ channels and widespread neuronal hyperpolarization [1]. The hyperpolarization may be due to opening of K+ channels responding to acute changes in local concentrations of ATP, H+ or Ca2+, or it may reflect altered nonheme metalloprotein association with and regulation of specific K+ channels [2]. This response, presumably protective, however fails to preserve high-energy phosphate levels in tissue as concentrations of phospho-creatine (PCr) and ATP fall within minutes after ischemia... 

The discovery that NO and CO are important messenger molecules in the mammalian brain and exert their effect by binding to metalloprotein receptors will certainly provoke increased interest in the area. ... 

Prange et al. analyzed the isoforms of metallothioneins in human brain cytosol with capillary electrophoresis (CE) coupled to ICP-SFMS (inductively coupled plasma-sector field mass spectrometry). In the study, three metal-lothionein isoforms were separated by CE, and the enriched isotopes of Cu, Zn, Cd, and were mixed as a specific-unspecific spiking solution finally, the Cu, Zn, Cd, and S in metallothioneins were quantified with IDA. They found that the levels of MT-3 and MT-1 were lower in the brain samples from the patients with Alzheimer s disease in comparison with the controls (see Figure 4.8). The results indicated that quantification of metalloproteins gave additional information on its relationship with Alzheimer s disease. ... 

D. E. K. Sutherland and M. J. Stillman, Mammalian MetaUothioneins, in Brain Diseases and Metalloproteins, ed. D. R. Brown, CRC Press, 2012, p. 81. A. Suzuki and T. Oku, Electronic Stmcture and Magnetic Properties of NdJCgo - SWCNT, in Electronic Properties of Carbon Nanotubes, ed. 

This article focuses on how the marked increase in the steady-state levels of metals (iron, copper and zinc) in the AD brain contributes to gene expression with deleterious consequences for neuronal survival [3]. Certainly APP mRNA translational control by iron (Rogers et al., 2002) and APP gene transcriptional control by copper [1] each provide new genetic support for the model that APP is a metalloprotein with an integral role in metal metabolism. 

An elucidation of the mechanisms of brain iron homeostasis, as outlined in figure 1, will help our understanding of AD especially since iron binds to Ap-peptide and enhances beta-amyloid toxicity [35-38]. Excess iron accumulation is a consistent observation in the AD brain. As discussed above, patients with hemochromatosis are at risk developing AD at an earlier age [2]. Brain autopsy samples from AD patients have elevated levels of ferritin iron, particularly in the neurons of the basal ganglia [39] and most amyloid plaques contain iron and ferritin-rich cells [40]. Clinically there is a reported decrease in the rate of decline in AD patients who were treated with the intramuscular iron chelator, desferrioxamine [41]. Iron enhances cleavage of the Ap-peptide domain of APP by the metalloprotease alpha secretase [42, 43]. Part of the protective effect of the major cleavage product of APP, APP(s), may derive from its capacity to scavange metals to diminish metal-catalyzed oxidative stress to neuronal cells [44]. APP is, itself, a metalloprotein [4]. 

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