title: The processing and biological function of the human amyloid precursor protein (APP): lessons from different cellular models.
abstract: One of the major neuropathological hallmarks of Alzheimer's disease is the presence of senile plaques in vulnerable regions of CNS. These plaques are formed of aggregated amyloid peptide. Amyloid peptide is released by the cleavage of its precursor (APP). The establishment of cell lines expressing human APP allowed to characterize both amyloidogenic and non-amyloidogneic pathways of APP catabolism and to identify some of the proteins involved in this processing (known as secretases). This led to a better comprehension of amyloid peptide production, which needs to be further characterized since gamma-secretase is as yet not identified; moreover, we still lack a clear overview of the interactions between APP and other proteins promoting Alzheimer's disease (tau, presinilinsellipsis). An important limitation of these cell lines for studying the mechanisms involved in Alzheimer's disease is supported by the observation that human APP expression does not modify transfected cells survival. The infection of primary neuronal cultures with full-length human APP indicates that APP expression induces neuronal apoptosis by itself; this neurotoxicity does not rely on extracellular production of APP derivatives (secreted APP, amyloid peptide). It is now essential to understand, in neuronal models, the production, localization and involvement of amyloid peptide in neurodegenerative processes.
authors.affiliation: Laboratoire Pharmacologie Expérimentale, UCL, FARL 5410, av Hippocrate 54, B-1200, Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Kienlen-Campard
authors.forename: B
authors.initials: B
authors.lastname: Tasiaux
authors.forename: J N
authors.initials: JN
authors.lastname: Octave
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology; D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D009474:Neurons / Q000378:metabolism; D051381:Rats
chemical_list: D016564:Amyloid beta-Protein Precursor