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Soluble alpha-APP (sAPPalpha) regulates CDK5 expression and activity in neurons

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Item Type:Article
Title:Soluble alpha-APP (sAPPalpha) regulates CDK5 expression and activity in neurons
Creators Name:Hartl, D. and Klatt, S. and Roch, M. and Konthur, Z. and Klose, J. and Willnow, T.E. and Rohe, M.
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.
Keywords:Amyloid beta-Protein Precursor, Cultured Cells, Cyclin-Dependent Kinase 5, Mass Spectrometry, Neurons, Two-Dimensional Gel Electrophoresis, Animals, Mice
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science (U.S.A.)
Volume:8
Number:6
Page Range:e65920
Date:11 June 2013
Official Publication:https://doi.org/10.1371/journal.pone.0065920
PubMed:View item in PubMed

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