title: Soluble alpha-APP (sAPPalpha) regulates CDK5 expression and activity in neurons.
abstract: A growing body of evidence suggests a role for soluble alpha-amyloid precursor protein (sAPPalpha) in pathomechanisms of Alzheimer disease (AD). This cleavage product of APP was identified to have neurotrophic properties. However, it remained enigmatic what proteins, targeted by sAPPalpha, might be involved in such neuroprotective actions. Here, we used high-resolution two-dimensional polyacrylamide gel electrophoresis to analyze proteome changes downstream of sAPPalpha in neurons. We present evidence that sAPPalpha regulates expression and activity of CDK5, a kinase that plays an important role in AD pathology. We also identified the cytoprotective chaperone ORP150 to be induced by sAPPalpha as part of this protective response. Finally, we present functional evidence that the sAPPalpha receptor SORLA is essential to mediate such molecular functions of sAPPalpha in neurons.
authors.affiliation: Institute for Medical Genetics and Human Genetics, Charité - University Medicine, Berlin, Germany. daniela.hartl@charite.de
authors.forename: Daniela
authors.initials: D
authors.lastname: Hartl
authors.forename: Stephan
authors.initials: S
authors.lastname: Klatt
authors.forename: Manfred
authors.initials: M
authors.lastname: Roch
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Konthur
authors.forename: Joachim
authors.initials: J
authors.lastname: Klose
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Willnow
authors.forename: Michael
authors.initials: M
authors.lastname: Rohe
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D051360:Cyclin-Dependent Kinase 5