Identification and characterisation of the novel amyloid-beta peptide-induced protein p17.
Amyloid-beta peptide (Abeta) achieves neurodegeneration through unknown mechanisms. To elucidate some of these mechanisms, we conducted a cDNA subtraction analysis of Abeta-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 Abeta-mediated pro-apoptotic pathways in AD.
Nehar
Saheen
S
Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Mishra
Manisha
M
Heese
Klaus
K
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C544750:p17 amyloid-beta peptide-induced protein, human; C544751:p17 amyloid-beta peptide-induced protein, mouse