Acetylcholinesterase Modulates Presenilin-1 Levels and γ-Secretase Activity

Activation and intrinsic γ-secretase activity of presenilin 1

Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; Department of Pharmacology, Department of Physiology, Biophysics and Systems Biology, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021; Center for Molecular Neurobiology, University of Chicago, Chicago, IL 60637; and Department of Chemical Engineering and ...

Presenilin/γ-Secretase and Inflammation

Presenilins (PS) are the catalytic components of gamma-secretase, an aspartyl protease that regulates through proteolytic processing the function of multiple signaling proteins. Specially relevant is the gamma-secretase-dependent cleavage of the beta-amyloid precursor protein (APP) since generates the beta-amyloid (Abeta) peptides that aggregate and accumulate in the brain of Alzheimer's diseas...

Podoplanin is a substrate of presenilin-1/γ-secretase.

Podoplanin (PDPN) is a mucin-like transmembrane glycoprotein that plays an important role in development and cancer. Here, we provide evidence that the intracellular domain (ICD) of podoplanin is released into the cytosol following a sequential proteolytic processing by a metalloprotease and γ-secretase. Western blotting and cell fractionation studies revealed that HEK293T and MDCK cells transf...

Presenilin 2 Is the Predominant γ-Secretase in Microglia and Modulates Cytokine Release

Presenilin 1 (PS1) and Presenilin 2 (PS2) are the enzymatic component of the γ-secretase complex that cleaves amyloid precursor protein (APP) to release amyloid beta (Aβ) peptide. PS deficiency in mice results in neuroinflammation and neurodegeneration in the absence of accumulated Aβ. We hypothesize that PS influences neuroinflammation through its γ-secretase action in CNS innate immune cells....

Presenilin-Dependent γ-Secretase-Like Intramembrane Cleavage of ErbB4