Amyloid enriched proteins

The mechanism of AD pathogenesis still remains unclear. However, one mechanism, amyloid (3 (A(3) accumulation, may be due to the disturbance in metal homeostasis in AD brains [Strausak et al., 2001]. A(3 peptides are the major constituents of the amyloid core of senile plaques, which are derived from the amyloid precursor protein (APP) and are secreted into extracelluar spaces. Both APP and A(3 contain a copper-binding domain [Hesse et al., 1994 Atwood et al., 1998]. High concentrations of copper, zinc, and iron have been found within the amyloid deposits in AD brains [Lovell et al., 1998], A(3 peptides can be rapidly precipitated by copper under mildly acidic conditions and by zinc at low physiological (submicromolar) concentrations [Bush et al., 1994], An age-dependent binding between A(3 peptides with excess brain metals (copper, iron, and zinc) induces A(3 peptides to precipitate into metal-enriched plaques [Bush, 2002],... 

Other IRRAS applications to peptides and proteins. In addition to the pulmonary surfactant system, a variety of other applications employing IRRAS to study peptide and protein conformation and orientation have appeared. The secondary structure conversion of the amyloid (prion)-protein in the normal form into the abnormal form is the main cause of several human and animal diseases, such as Alzheimer s disease [68]. The secondary structure of the first 40 residues of the amyloid protein was detected by circular dichroism (CD) in aqueous solution and with IRRAS at the interface. A stable /1-sheet-enriched state of the amyloid is formed at the air-water interface, in contrast to the initial bulk solution containing high a-helix/random coil and low /l-sheet parts. The change in the pH going from bulk (alkaline pH) to the interface (neutral or slightly acidic pH) can have effects on the conformation at the interface. Another alternative might be the intrinsic hydrophobicity of the air-water interface, which is a hydrophobic-hydrophilic system with air as the hydrophobic part. 

Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, Cole GM (2005) A diet enriched with the omega-3 fatty add docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosd 25 3032-3040 Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J (2000) Human aspartic protease memapsin 2 cleaves the )-secretase site of P-amyloid precursor protein. Proc Natl Acad Sci USA 97 1456-1460... 

Alzheimer s disease (AD) is one of the most common forms of dementia that affect the elderly population. The histopathological hallmarks of AD are extracellular deposits known as neuritic amyloid plaques and intraneuronal inclusions composed of hyperphosphorylated tangles enriched with tau proteins.1 The principal component of the neuritic plaques is aggregation of amyloid (A0), which is likely to play a role in the neurodegenerative process. The relative contribution of the various forms (soluble dimers, small oligomers, protofibrils, and fibrils) of A0 to neuronal... 

Most proteomics analyses involve 2-D electrophoresis and MALDl-TOF MS steps, as this approach allows for a reliable quantification of changes in protein levels. In one study, the LC-MS/MS approach was used for the detection of proteins enriched in amyloid plaques in the AD brain (liao et al., 2004). Employing the former proteomic approach, levels of about 100 proteins were foimd to be changed in the AD brain and cerebrospinal fluid (CSF) in comparison with the control brain and CSF, respectively (Table 15.1). These proteins have various functions, mainly involved in neurotransmission, guidance, signal transduction, metabolism, detoxification, and conformational changes. The CSF proteins are plasma proteins. 

Coronin, achn binding protein Enriched in amyloid plaques Liao et al. 2004... 

Using LC-MS/MS, Liao et al. (2004) identified 26 brain proteins enriched in amyloid plaques excised with laser capture microdissection from AD brains. 

Koushika SP, Soller M, White K (2000) The neuron-enriched splicing pattern of Drosophila erect wing is dependent on the presence of ELAV protein. Mol Cell Biol 20 1836-1845 Kremer EJ, Pritchtird M, Lynch M, Yu S, Holman K et al (1991) Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science 252 1711-1714 LaFetla EM, Green KN, Oddo S (2007) Intracellular amyloid-beta in Alzheimer s disease. Nat Rev Neurosd 8 499-509... 

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