Soluble Alpha-APP (sAPPalpha) Regulates CDK5 Expression and Activity in Neurons

被引：26

作者：

Hartl, Daniela ^{[1
]}

Klatt, Stephan ^{[2
,3
]}

Roch, Manfred ^{[1
]}

Konthur, Zoltan ^{[2
,4
]}

Klose, Joachim ^{[1
]}

Willnow, Thomas E. ^{[5
]}

Rohe, Michael ^{[5
]}

机构：

[1] Charite, Inst Med Genet & Human Genet, D-13353 Berlin, Germany

[2] Max Planck Inst Mol Genet, D-14195 Berlin, Germany

[3] Free Univ Berlin, Fac Biol Chem & Pharm, Berlin, Germany

[4] Max Planck Inst Colloids & Interfaces, Potsdam, Germany

[5] Max Delbruck Ctr Mol Med, Berlin, Germany

来源：

PLOS ONE | 2013年 / 8卷 / 06期

关键词：

AMYLOID PRECURSOR PROTEIN; CYCLIN-DEPENDENT KINASE-5; SORTILIN-RELATED RECEPTOR; ALZHEIMERS-DISEASE; HIPPOCAMPAL-NEURONS; SECRETED FORMS; NEURODEGENERATIVE DISEASES; TAU PHOSPHORYLATION; CEREBROSPINAL-FLUID; ADULT NEUROGENESIS;

D O I：

10.1371/journal.pone.0065920

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：7

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