Identification and characterisation of the novel amyloid-beta peptide-induced protein p17

Abstract

Amyloid-beta peptide (Aβ) achieves neurodegeneration through unknown mechanisms. To elucidate some of these mechanisms, we conducted a cDNA subtraction analysis of Aβ-mediated neurotoxicity in neuronal cells and observed an up-regulation of the novel gene p17. The p17 protein was also found elevated in Alzheimer’s disease (AD) mouse model. Here, we characterised p17 primarily in cell lines with respect to its localisation, function and physiological expression. We discovered that p17 acts downstream of protein kinase C and inhibits the tyrosine receptor kinase B–brain-derived neurotrophic factor (TrkB–BDNF) pathway. It impedes survival factors and enhances amyloid precursor protein expression thus suggesting its involvement in the Aβ-mediated pro-apoptotic pathways in AD.