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Item Type: | Article |
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Title: | Soluble alpha-APP (sAPPalpha) regulates CDK5 expression and activity in neurons |
Creators Name: | Hartl, D., Klatt, S., Roch, M., Konthur, Z., Klose, J., 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 |
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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