Università della Svizzera italiana

Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

Revandkar, Ajinkya ; Perciato, Maria Luna ; Toso, Alberto ; Alajati, Abdullah ; Chen, Jingjing ; Gerber, Hermeto ; Dimitrov, Mitko ; Rinaldi, Andrea ; Delaleu, Nicolas ; Pasquini, Emiliano ; D’Antuono, Rocco ; Pinton, Sandra ; Losa, Marco ; Gnetti, Letizia ; Arribas, Alberto ; Fraering, Patrick ; Bertoni, Francesco ; Nepveu, Alain ; Andrea Alimonti

In: Nature communications, 2016, vol. 7, p. 13719

Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours ...

Université de Fribourg

The metalloprotease ADAMTS4 generates N-truncated Aβ4–x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer’s disease

Walter, Susanne ; Jumpertz, Thorsten ; Hüttenrauch, Melanie ; Ogorek, Isabella ; Gerber, Hermeto ; Storck, Steffen E. ; Zampar, Silvia ; Dimitrov, Mitko ; Lehmann, Sandra ; Lepka, Klaudia ; Berndt, Carsten ; Wiltfang, Jens ; Becker-Pauly, Christoph ; Beher, Dirk ; Pietrzik, Claus U. ; Fraering, Patrick C. ; Wirths, Oliver

In: Acta Neuropathologica, 2019, vol. 137, no. 2, p. 239–257

Brain accumulation and aggregation of amyloid-β (Aβ) peptides is a critical step in the pathogenesis of Alzheimer’s disease (AD). Full-length Aβ peptides (mainly Aβ1–40 and Aβ1–42) are produced through sequential proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. However, studies of autopsy brain samples from AD patients have demonstrated that a...

Université de Fribourg

The Alzheimer’s disease γ-secretase generates higher 42:40 ratios for β-amyloid than for p3 peptides

Siegel, Gabriele ; Gerber, Hermeto ; Koch, Philipp ; Bruestle, Oliver ; Fraering, Patrick C. ; Rajendran, Lawrence

In: Cell Reports, 2017, vol. 19, no. 10, p. 1967–1976

Alzheimer’s disease is characterized by intracerebral deposition of β-amyloid (Aβ). While Aβ40 is the most abundant form, neurotoxicity is mainly mediated by Aβ42. Sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases gives rise to full-length Aβ (Aβ1-x) and N-terminally truncated Aβ′ (Aβ11-x) whereas cleavage by α- and γ-secretases leads to the shorter...