Regulated intramembrane proteolysis of the amyloid precursor protein (APP) by the protease activities α-, β- and γ-secretase controls the generation of the neurotoxic amyloid β peptide. APLP2, the amyloid precursor-like protein 2, is a homolog of APP, which shows functional overlap with APP, but lacks an amyloid β domain. Compared to APP, less is known about the proteolytic processing of APLP2,...

Passive immunization against misfolded toxic proteins is a promising approach to treat neurodegenerative disorders. For effective immunotherapy against Alzheimer's disease, recent clinical data indicate that monoclonal antibodies directed against the amyloid-β peptide should be administered before the onset of symptoms associated with irreversible brain damage. It is therefore critical to devel...

OBJECTIVES This work deals with the conformational and thermal characterization of a synthetic peptide (S4) released during the proteolysis of human tropoelastin by the matrix metalloproteinase-12 that was shown to form amyloid-like fibres under certain conditions. MATERIALS AND METHODS S4 peptides were synthesized by solid-phase methodology and aggregated in solution at 80°C. Fourier transfo...

Patients with Alzheimer's disease show age-related cognitive decline. Postmortem autopsy of their brains shows the presence of large numbers of senile plaques, whose major component is the β-amyloid peptide. The β-amyloid peptide is a cleavage product of the amyloid precursor protein (APP). In addition to the neurodegeneration associated with β-amyloid aggregation in Alzheimer's disease patient...

BACKGROUND Beside neurofibrillary tangles, amyloid plaques are the major histological hallmarks of Alzheimer's disease (AD) being composed of aggregated fibrils of β-amyloid (Aβ). During the underlying fibrillogenic pathway, starting from a surplus of soluble Aβ and leading to mature fibrils, multiple conformations of this peptide appear, including oligomers of various shapes and sizes. To furt...

The inverse sequences of naturally occurring proteins display different folding and structural properties fail to retain the functions native despite identical fundamental features, such as amino acid composition, hydrophobicity, etc. To gain insight into physical mechanisms underlying secondary structure formation aggregation direct retro amyloidogenic peptides, we probed fibrillogenesis accom...

The peptide Boc-Val-Phe-OMe 1 bearing sequence similarity with the central hydrophobic cluster (CHC) of Alzheimer's Aβ(18-19) peptide self-assembles to produce amyloid-like straight unbranched fibrils as examined by atomic force microscopy and Congo red assay. Single crystal X-ray diffraction offers the atomic level structure of the supramolecular parallel β-sheet aggregation and antiparallel s...

Background: The British Precursor Protein (BRI2) influences Amyloid Precursor Protein metabolism. Results: BRI2 lowers β-amyloid peptide levels by increasing levels of secreted insulin degrading enzyme (IDE) in both cells and mice. Conclusion: BRI2 as a receptor protein regulates IDE levels and in turn promotes βamyloid degradation. Significance: Targeting the regulation of IDE may lead to new ...