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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.

SUBMITTER: Hartl D

PROVIDER: S-EPMC3679172 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Hartl Daniela D Klatt Stephan S Roch Manfred M Konthur Zoltan Z Klose Joachim J Willnow Thomas E TE Rohe Michael M

PloS one 20130611 6

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 ev ...[more]

PMID: 23776568

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