Die Rolle von sekretiertem APP bei der Modulation des Akt Signalwegs und der Neuroprotektion

• Antragsteller: Professor Dr. Donat Kögel
• Fachliche Zuordnung: Molekulare und zelluläre Neurologie und Neuropathologie
• Förderung: Förderung von 2014 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 258499424

• Erstellungsjahr: 2019

Zusammenfassung der Projektergebnisse

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.

Projektbezogene Publikationen (Auswahl)

• (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
  
• 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
  
• (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
  
• 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