The role of secreted APP in modulation of the Akt survival signaling pathway and neuroprotection

• Applicant: Professor Dr. Donat Kögel
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 258499424

• Final Report Year: 2019

Final Report Abstract

We were able to show that modulation of proteostasis and activation of Akt survival signaling are functionally uncoupled biological properties of sAPPα that act via distinct signal transduction mechanisms. While the major molecular mechanisms in sAPPα-mediated Akt activation have been elucidated in this study, the exact molecular players involved in sAPPα-dependent modulation of proteostasis remain to be identified in future studies.

Publications

• (2014). Holo-APP and G-protein-mediated signaling are required for sAPPα-induced activation of the Akt survival pathway. Cell Death Dis. 28;5:e1391
  Milosch N, Tanriöver G, Kundu A, Rami A, François JC, Baumkötter F, Weyer SW, Samanta A, Jäschke A, Brod F, Buchholz CJ, Kins S, Behl C, Müller UC, Kögel D
  (See online at https://doi.org/10.1038/cddis.2014.352)
• The physiological role of APP in the activation of neuroprotective signaling mechanisms (2014)
  Nelli Milosch
  
• (2015). The cleavage product of amyloid-β protein precursor sAβPPα modulates BAG3- dependent aggresome formation and enhances cellular proteasomal activity. J Alzheimers Dis. 44:879-96
  Renziehausen J, Hiebel C, Nagel H, Kundu A, Kins S, Kögel D, Behl C, Hajieva P
  (See online at https://doi.org/10.3233/JAD-140600)
• (2017). Modulation of BAG3 Expression and Proteasomal Activity by sAPPα Does Not Require Membrane-Tethered Holo-APP. Mol Neurobiol. 53:5985-5994
  Kundu A, Milosch N, Antonietti P, Baumkötter F, Zymny A, Müller UC, Kins S, Hajieva P, Behl C, Kögel D
  (See online at https://doi.org/10.1007/s12035-015-9501-y)
• The role of the amyloid precursor protein (APP) in protein homeostasis and neuroprotection (2017)
  Arpita Kundu
  
• (2018). Role of APP Interactions with Heterotrimeric G Proteins: Physiological Functions and Pathological Consequences. Front Mol Neurosci. 10:3
  Copenhaver PF, Kögel D
  (See online at https://doi.org/10.3389/fnmol.2017.00003)