Plaque-related proteins

The exact cause of Alzheimer s disease remains unknown, although a number of factors have been suggested. These include metabolism and regulation of amyloid precursor protein, plaque-related proteins, tau proteins, zinc, copper, and aluminum [1]. 

Kockx, M.M., De Meyer, G.R., Muhiing, J., Jacob, W., Bull, H., and Herman, A.G.., 1998fc, Apoptosis and related proteins in different stages ofhuman atherosclerotic plaques. Circulation 97 2307-2315. 

Interest in protein and peptide interactions with phospholipid membranes and surfaces originates from its importance for both key biophysical processes (eg, atherosclerosis, Alzheimer s, and other plaque-related diseases) and a wide range of biomedical applications. For example, control of protein/peptide adsorption allows reduction of inflammation and other unwanted biopharmaceutical effects in phospholipid-based biomaterials and dmg delivery but also improved signal-to-noise in biosensors and... 

Even less well characterized are several other Gla proteins from a variety of tissues. Kidney contains nephrocalcin, with just two or three Gla residues, which may be involved in renal calcium transport (another important function that may be impaired by vitamin K deficiency in man). Atherocalcin, or plaque Gla protein, may be related or even identical to MGP. Proline-rich Gla proteins PRGP-1 and PRGP-2 are found predominantly in the spinal cord and thyroid gland, respectively, but their functions are unknown. Gla proteins occur in most vertebrates and also in molluscs, so their evolutionary appearance in the animal kingdom is probably quite ancient in origin. 

As early as 1953 Goodman noted that iron deposits were frequendy seen in association with amyloid plaques of Alzheimer s disease (AD) and that the disease may be due to a disturbance in the cerebral metabolism of iron... (91). The possibility of iron involvement in the pathogenesis of AD is consistent with the prevailing view that aggregations of amyloid A-beta are the proximate cause of this disease. There have been several reports of iron and iron-related proteins, such as ferritin, as components of senile plaques (92-94). A number of MRI and... 

CD has been used extensively in studies of peptides related to Alzheimers disease, although studies of the amyloid plaques associated with the disease are precluded by their insolubility. 211 A peptide consisting of 39-43 residues is the principal component of amyloid deposits that are found in the brains of Alzheimers patients. This peptide, called A4, 3-peptide, or 3AP for (3-amyloid peptide, is derived by proteolytic cleavage of a protein called amyloid protein (APP). The mechanism of aggregation of (3AP is clearly of great interest. 

Magaki et al. [2007] measured the levels of loosely bound, nonheme, and total iron and copper in the frontal cortex and hippocampus of patients with mild-moderate AD (n = 3), severe AD (n = 8), and dementia with Lewy bodies (DLB, n = 6). Additionally, the expression of iron regulatory protein 2 (IRP2) was examined in relation to the pathological hallmarks of AD, that is, 5 amyloid plaques, neurofibrillary tangles (NFT), and Lewy bodies. A significant decrease of loosely bound iron was found in the hippocampal white matter of both mild-moderate and severe AD patients and a trend toward increased... 

Plaque stabilization Reduced CD40 expression and CD40-related activation of vascular cells Reduced leukocyte-endothelial cell interactions Reduced C-reactive protein levels and proinflammatory cytokines Inhibition of LDL oxidation Reduced cytotoxicity of T-lymphocytes Inhibition of proinflammatoiy T helper 1 cell development and augmentation of anti-inflammatoy T helper 2 cell development Reduced oxidized LDL uptake... 

The histopathological characteristics of the brain in Alzheimer s diseases (AD) are the presence of intraneuronal neurofibrillary tangles (NFTs), extraneuronal amyloid-rich senile plaques, and a massive loss of neurons of the telencephalon. Although amyloid proteins are unique to senile plaques, several components are common to both senile plaques and NFTs hyperphosphory-lated tau proteins, ubiquitin, a 1-antichymotrypsin, apolipoprotein E, heparan sulfate proteoglycans, and Al and Fe [29]. Recent reports on Al and Fe transport mechanisms and the relation between them in AD are reviewed below. 

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