Amyloid protein detection

Lashuel, H. A., Petre, B. M., Wall, J., Simon, M., Nowak, R. J., Walz, T., and Lansbury, P. T., Jr. (2002). Alpha-synuclein, especially the Parkinson s disease-associated mutants, forms pore-like annular and tubular protofibrils./. Mol. Biol. 322,1089-1102. LeVine, H. (1993). Thioflavine T interaction with synthetic Alzheimer s disease beta-amyloid peptides Detection of amyloid aggregation in solution. Protein Sci. 2, 404—410. Lin, H., Bhatia, R., and Lai, R. (2001). Amyloid beta protein forms ion channels Implications for Alzheimer s disease pathophysiology. FASEB J. 15, 2433-2444. Lorenzo, A., and Yankner, B. A. (1994). Beta-amyloid neurotoxicity requires fibril formation and is inhibited by Congo red. Proc. Natl. Acad. Sci. USA 91, 12243-12247. Luhrs, T., Ritter, C., Adrian, M., Riek-Loher, D., Bohrmann, B., Dobeli, H., Schubert, D., and Riek, R. (2005). 3D structure of Alzheimer s amyl o id-( be la) (1—12) fibrils. Proc. Natl. Acad. Sci. USA 102, 17342-17347. 

LA-ICP-MS has been developed for the detection and imaging of (3-amyloid protein in immuno-histochemical sections from the brain of a transgenic mouse model of Alzheimer s disease. The distribution of (3-amyloid deposits in tissue based on measurements of Eu and Ni coupled antibodies has been studied by McLeods group.170... 

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. 

LeVine H. Ill Thioflavin-T interaction with syndietic Alzheimers-disease beta amyloid peptides- detection of amyloid aggregation in solution. Protein Sci. 1993 2 404 10. 

NGF is secreted by neurones in the hippocampus and is transported via the fimbria fornix to basal forebrain cholinergic neurones. In Alzheimer s disease, a disruption in NGF production could explain the degenerations of the nucleus basalts of Meynert. In Alzheimer s disease, neurones are only lost from the rostral part of the locus ceruleus where neurones are responsive to cortical neurotrophic factors [85], Actually, it appears that NGF production in the brain of patients with Alzheimer s disease is normal. Inversely, decreased expression of brain-derived neurotrophic factor (BDNF) has been detected in post-mortem Alzheimer patients brains. Furthermore, NGF receptor density has been shown to be significantly reduced. Loss of neurotrophin receptors may result in neuronal degeneration, as available factors are unable to convey trophic support to dependent neurones. In addition, possible interactions between trophic factors and amyloid protein deposits have been investigated. Administered in vitro, NGF would potentiate -amyloid neurotoxicity. The gamma subunit of the 75 NGF complex appears to possess peptidase activity and could contribute to APP mis-metabo-lism [86]. 

Amyloid proteins related to immunoglobulin possess individually specific (idiotypic) antigenic determinants i.e., such amyloid proteins from different individuals possess unique primary structures. Idiotypic determinants characteristic of a given amyloid protein can sometimes be detected in the serum of the same individual. In addition, however, amyloid proteins of a given type (it or X) frequently have shared antigenic determinants (120,124,126). Antiserum directed to an amyloid protein will, in general, cross-react weakly with normal L chains of the same type. It seems likely that these cross-reactions are attributable, in the case of the smaller amyloid proteins, to shared V region sequences. 

Finally, paramagnetic relaxation was used in order to determine the effects of metal ion association with amyloid fibrils. Several specific sites of Cu were detected in the amyloid protein AjS(l O) using PRE and shift perturbation data firom solid-state NMR, and corroborated using detailed molecular dynamics (MD) models. It was also found by this means that the amyloid fibril structure is not significantly altered by Cu binding. This smdy is particularly interesting on account of its medical pertinence, as Cu° is often found at elevated concentration in cells containing Alzheimers plaques [103]. 

Thirunavukkuarasu, S. Jares-Eiijman, E. A. Jovin, T. M. Multiparametric fluorescence detection of early stages in the amyloid protein aggregation of pyrene-labeled a-synuclein. J. Mol. Biol. 2008, 378, 1064-1073. 

Lomakin A, Chung DS, Benedek GB, Kirschner DA, Teplow DB. On the nucleation and growth of amyloid beta protein fibrils detection of nuclei... 

Walsh DM, Lomakin A, Benedek GB, Condron MM, Teplow DB. Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate. J Biol Chem 1997 272 22364-22372. 

Lomakin, A., Chung, D. S., Benedek, G. B., Kirschner, D. A., and Teplow, D. B. (1996). On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants. Proc. Natl. Acad. Sci. USA 93, 1125-1129. 

In view of the consideration that /(-solenoids and /(-arcades may also be structural elements of amyloid fibrils (Kajava et al., 2004 Lazo and Downing, 1998 Margittai and Langen, 2004 Pickersgill, 2003), sequence-based detection and structure prediction of /(-solenoid proteins are pertinent to the identification of amyloidogenic sequences and the elucidation of amyloid fibril structures. As with /(-solenoid domains, amyloidogenic regions of... 

Use of the anionic CP allowed for detection of amyloid fibril formation in both bovine insulin and chicken lysozyme proteins (Fig. 16). The polymer in buffer... 

Fig. 16 (a) Description of the detection of amyloid fibrils in proteins with an anionic conjugated polymer, PTAA. (b) Emission spectra (bottom) of PTAA-Native bovine insulin (filled square) and PTAA-amyloid fibrillar bovine insulin (x). (c) Kinetics of insulin amyloid fibril formation monitored by PTAA fluorescence [29]... 

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