title: APP and APLP1 are degraded through autophagy in response to proteasome inhibition in neuronal cells.
abstract: Amyloid beta (Aβ) precursor protein (APP) is a key protein in the pathogenesis of Alzheimer's disease (AD). Both APP and its paralogue APLP1 (amyloid beta precursor-like protein 1) have multiple functions in cell adhesion and proliferation. Previously it was thought that autophagy is a novel beta-amyloid peptide (Aβ)-generating pathway activated in AD. However, the protein proteolysis of APLP1 is still largely unknown. The present study shows that APLP1 is rapidly degraded in neuronal cells in response to stresses, such as proteasome inhibition. Activation of the endoplasmic reticulum (ER) stress by proteasome inhibitors induces autophagy, causing reduction of mature APLP1/APP. Blocking autophagy or JNK stress kinase rescues the protein expression for both APP and APLP1. Therefore, our results suggest that APP/APLP1 is degraded through autophagy and the APLP1 proteolysis is mainly mediated by autophagy-lysosome pathway.
authors.affiliation: Medical College of Chongqing Medical University, Chongqing, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhou
authors.forename: Theo
authors.initials: T
authors.lastname: van Laar
authors.forename: Huizhe
authors.initials: H
authors.lastname: Huang
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D055550:Protein Stability; D051381:Rats
chemical_list: D016564:Amyloid beta-Protein Precursor; C078201:Aplp1 protein, mouse; D007976:Leupeptins; D061988:Proteasome Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde