..., the rigor of those studies, and the critical knowledge gaps of relationships between APP, Aβ, and mitochondria. Figure 1. APP processing pathways. ( A ) Non-amyloidogenic APP processing. First, APP is cleaved by ADAM10 leading to the production of C83 and sAPPα. Next, C83 is cleaved γ-secretase...

... receptors by membrane-bound proteases and the γ-secretase protease complexes. Proteolysis enables the liberation of soluble receptor ectodomains and the generation of intracellular receptor cytoplasmic domain fragments. The combined and sequential enzymatic activity has been defined as regulated...

...@cbm.uam.es ). 30 8 2010 © The Authors Journal compilation © 2011 Biochemical Society 2011 a disintegrin and metalloproteinase (ADAM) regulated intramembrane proteolysis (RIP) γ-secretase shedding tetraspanin Proteolytic release of the ectodomains of transmembrane proteins...

...) and APP (amyloid precursor protein), in patients with FAD (familial AD) has made an important contribution towards an understanding of the disease aetiology; however, a complete molecular mechanism is still lacking. Both presenilins belong to the γ-secretase complex, and serve as the catalytic entity...

... proteases (β- and γ-secretases) that are leading candidates for therapeutic intervention. APP is a member of a multigene family that includes APLP1 (amyloid precursor-like protein 1) and APLP2. Both APLPs are processed in a manner analogous to APP, with all three proteins subject to ectodomain shedding...

... neuroprotective effects for the treatment of neurodegenerative diseases. Like amyloid precursor protein and Notch, p75 is a substrate for γ-secretase cleavage. The p75 receptor undergoes an α-secretase-mediated release of the extracellular domain followed by a γ-secretase-mediated intramembrane cleavage. Cleavage...

...T. Raemaekers; C. Esselens; W. Annaert Presenilin 1 plays a central catalytic role in the γ-secretase processing of amyloid precursor protein, Notch and many other substrates. However, this core component clearly mediates independently several other physiological roles in the cell/neuron. Besides...