amyloid-beta-peptides and Cadaver

Recent studies have reported that many proteases, besides the canonical α-, β-, and γ-secretases, cleave the amyloid precursor protein (APP) and modulate β-amyloid (Aβ) peptide production. Moreover, specific APP isoforms contain Kunitz protease-inhibitory domains, which regulate the proteolytic activity of serine proteases. This prompted us to investigate the role of matriptase, a member of the type II transmembrane serine protease family, in APP processing. Using quantitative RT-PCR, we detected matriptase mRNA in several regions of the human brain with an enrichment in neurons. RNA sequencing data of human dorsolateral prefrontal cortex revealed relatively high levels of matriptase RNA in young individuals, whereas lower levels were detected in older individuals. We further demonstrate that matriptase and APP directly interact with each other and that matriptase cleaves APP at a specific arginine residue (Arg-102) both

Topics: Age Factors; Aged; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Brain; Cadaver; Cell Line; Computational Biology; Gene Expression Regulation, Enzymologic; Humans; Mutagenesis, Site-Directed; Mutation; Nerve Tissue Proteins; Neurons; Organ Specificity; Peptide Fragments; Prefrontal Cortex; Proteolysis; Recombinant Fusion Proteins; RNA, Messenger; Serine Endopeptidases; Substrate Specificity; Young Adult