A 109-amino-acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein contains a sequence, -RHDS-, that promotes cell adhesion.

摘要: Amyloid beta (A beta), the major constituent of fibrils composing senile plaques and vascular amyloid deposits in Alzheimer's disease (AD) related disorders, is a 39-42-residue self-aggregating degradation peptide larger multidomain membrane glycoprotein designated precursor protein (APP). An array biological functions has been assigned to different APP domains, including growth regulation, neurotoxicity, inhibitory activity serine proteinases promotion cell-cell cell-matrix interactions. A generated through an as-yet-unknown catabolic pathway that by-passes or inhibits cleavage within sequence. We have identified 16 kDa intermediate C-terminal fragment containing leptomeningeal vessels aged normal individuals AD patients by means its immunoreactivity with panel four anti-(APP C-terminal) antibodies, indicating processing. Previous studies indicated domain most likely be involved 109-amino-acid construct C109 sequence analogous (positions 587-695 APP695), similar length fragment, was found promote cell adhesion. By use synthetic peptides, this initially located extracellular 28 residues beta. Inhibition demonstrated RHDS (amino acids 5-8 beta, corresponding 601-604 APP695 responsible for adhesion-promoting activity. The interaction dependent on bivalent cations can blocked either tetrapeptides RGDS anti-(beta 1 integrin) antibody. Thus, integrin-like surface receptors, derivative proteolytic fragments may modulate