Amyloid β protein

Membrane-permeable inhibitor of Aβ (1-40) fibrillogenesis.

The pentapeptide Ac-LPFFD-NH? (iAβ5p) is an analog of product H-4876 with small chemical modifications which enhance its stability against proteolytic degradation. iAβ5p acts as a β-sheet breaker peptide and crosses the blood-brain barrier at a higher rate than most proteins and peptides known to be selectively taken up by the brain so that it is assumed that the peptide is being specifically transported to the brain. A significant increase in neuronal survival and decrease in brain inflammation associated with the reduction of amyloid plaques in two different transgenic Alzheimer`s disease (AD) models is additionally reported for iAβ5p.

This cyclized peptide which is homologous to the heparin-binding domain of APP, binds strongly to heparin and inhibits binding of ¹²?I-labeled APP to heparin (IC??= 10??M). The peptide blocks the heparan sulfate proteoglycan-dependent stimulatory effect of APP on neurite outgrowth.

Incubation of Ac-QKLVFF-NH? with the amyloid β-protein (1-40) inhibited polymerization of the amyloid β-protein (1-40) into amyloid fibrils. The peptide is thought to block the polymerization sites.

Experiments using sub-peptides of Aβ42 revealed that the epitope identified by the antibody A8, as described by Ying and coworkers, lies within the 1-6 region of Aβ. The antibody displays high affinity for soluble Aβ42 oligomers in the molecular weight range of 16.5-25 kDa, and detected target antigen in brain sections from senescence-accelerated SAMP 8 mice. Amidated or acetylated and amidated forms of the sequence were used for example for quantitative structure retention relationships (QSRR) experiments. The latter could allow prediction of reversed-phase high-performance liquid chromatography (HPLC) retention of peptides, as reported by Kaliszan and coworkers.

The peptide substrate APP (667-676), SEVKMDAEFR, corresponds to the wild-type amyloid precursor protein (APP) β-secretase cleavage site. SEVKMDAEFR has been used for assaying β-secretase activity.

Amyloid β/A4 Protein Precursor??? (740-770) corresponds to a C-terminal amyloid precursor protein (APP) fragment known as C31. This fragment is intracellularly generated by proteolytic cleavage of APP by caspases-8 and -9. C31 had a proapoptotic and a cytotoxic effect on neuronal cells and was shown to be present in brains of Alzheimer's disease (AD) patients. In cultured cells caspase cleavage of APP was induced by amyloid β-protein and the subsequent generation of C31 contributed to the apoptotic cell death associated with amyloid β-protein. Amyloid precursor binding protein BP1 (APP-BP1) a cell cycle protein which is increased in AD brain was demonstrated to bind to the C31 region of APP and to mediate APP-induced apoptosis.

Amyloid β-protein (10-35), YEVHHQKLVFFAEDVGSNKGAIIGLM, was used as a truncated peptide model for the full-length amyloid β-proteins (1-40) and (1-42) in high-resolution structural studies. In contrast to the full-length amyloid β-proteins, amyloid β-protein (10-35) allowed the controlled and reproducible formation of homogeneous fibrils from aqueous solutions of defined pH, ionic strength and soluble peptide concentration necessary for high-resolution structural studies.

The N-terminal Aβ fragments Aβ1-14, Aβ1-15 (H-6368), and Aβ1-16 (H-2958) are elevated in cell media and in CSF in response to γ-secretase inhibitor treatment. The presence of these small peptides is consistent with a catabolic amyloid precursor protein cleavage pathway by β- followed by α-secretase. It has been shown that Aβ1-14, Aβ1-15, and Aβ1-16 increase dose-dependently in response to γ-secretase inhibitor treatment while Aβ1-42 levels are unchanged.

Amyloid β-Protein (1-37) correlates moderately with Mini-Mental State Examination (MMSE) scores in Alzheimer disease.

Like Aβ (25-35) (H-1192), the Aβ fragment (1-38) destabilizes calcium homeostasis and renders human cortical neurones vulnerable to environmental insults.

Small quantities of Aβ37, 38 and 39 can be detected in CSF together with Aβ40, the most abundant Aβ homolog, Aβ42, and N-terminally truncated amyloid peptides. The relative amounts depend on the variant of Alzheimer's disease. The C-terminally truncated amyloid peptides are also found in amyloid plaques.

Compared to the inner salt, the HCl salt of Aβ42 aggregates more readily at pH 7.4.

Amyloid β-Protein (1-43) is more prone to aggregation and has higher toxic properties than the long-known Aβ1-42.

Precursor of the secreted amyloid β-protein (1-40) and (1-42). The identification of amyloid-β-protein (1-46) led to the identification of a zeta-cleavage site between the known γ- and ε-cleavage sites within the transmembrane domain of amyloid-β precursor protein (APP).

Experiments using sub-peptides of Aβ42 revealed that the epitope identified by the antibody A8, as described by Ying and coworkers, lies within the 1-6 region of Aβ. The antibody displays high affinity for soluble Aβ42 oligomers in the molecular weight range of 16.5-25 kDa, and detected target antigen in brain sections from senescence-accelerated SAMP 8 mice.

Experiments using sub-peptides of Aβ42 revealed that the epitope identified by the antibody A8, as described by Ying and coworkers, lies within the 1-6 region of Aβ. The antibody displays high affinity for soluble Aβ42 oligomers in the molecular weight range of 16.5-25 kDa, and detected target antigen in brain sections from senescence-accelerated SAMP 8 mice. Amidated or acetylated and amidated forms of the sequence were used for example for quantitative structure retention relationships (QSRR) experiments. The latter could allow prediction of reversed-phase high-performance liquid chromatography (HPLC) retention of peptides, as reported by Kaliszan and coworkers.

Amyloid β-Protein (16-20) is a five-amino acid fragment of the amyloid-β protein.