Results 31 to 40 of about 40,728 (191)

The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer's disease [PDF]

, 2015
Alzheimer's disease (AD) is the most common form of dementia in the elderly and its prevalence is set to increase rapidly in coming decades. However, there are as yet no available drugs that can halt or even stabilize disease progression. One of the main
Baillie, George S., Cameron, Ryan T., Hillert, Ellin-Kristina, MacLeod, Ruth   +3 more
core   +1 more source

In vitro validation of γ-secretase inhibitors alone or in combination with other anti-cancer drugs for the treatment of T-cell acute lymphoblastic leukemia

Haematologica, 2008
Background Activating NOTCH1 mutations are common in T-cell acute lymphoblastic leukemia. Inhibition of NOTCH1 signaling with γ-secretase inhibitors causes cell cycle block, but only after treatment for several days.
Kim De Keersmaecker, Idoya Lahortiga, Nicole Mentens, Cedric Folens, Leander Van Neste, Sofie Bekaert, Peter Vandenberghe, Maria D. Odero, Peter Marynen, Jan Cools   +9 more
doaj   +1 more source

A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP. [PDF]

, 2015
Clues to Alzheimer disease (AD) pathogenesis come from a variety of different sources including studies of clinical and neuropathological features, biomarkers, genomics and animal and cellular models. An important role for amyloid precursor protein (APP)
Cheng, Soan, Goldstein, Lawrence SB, Mobley, William C, Natera-Naranjo, Orlangie, Nguyen, Phuong, Pearn, Matthew L, Reyna, Sol M, Tanzi, Rudolph E, Wagner, Steven L, Weissmiller, April M, Wu, Chengbiao, Zhao, Xiaobei   +11 more
core   +2 more sources

Activation of an endothelial Notch1-Jagged1 circuit induces VCAM1 expression, an effect amplified by interleukin-1β [PDF]

, 2015
The Notch1 and Notch4 signaling pathways regulate endothelial cell homeostasis. Inflammatory cytokines induce the expression of endothelial adhesion molecules, including VCAM1, partly by downregulating Notch4 signaling.
Adesso, Laura, Alisi, Anna, Campese, Antonio Francesco, Ciarapica, Roberta, Giorda, Ezio, Gueguen, Marie, Kitajewski, Jan, Limon, Isabelle, Locatelli, Franco, Miele, Lucio, Panera, Nadia, Raimondi, Lavinia, Rota, Rossella, Screpanti, Isabella, Stifani, Stefano, Verginelli, Federica   +15 more
core   +7 more sources

Cholesterol-Dependent γ-Secretase Activity in Buoyant Cholesterol-Rich Membrane Microdomains

Neurobiology of Disease, 2002
Buoyant membrane fractions containing presenilin 1 (PS1), an essential component of the γ-secretase complex, and APP CTFβ, a γ-secretase substrate, can be isolated from cultured cells and brain by several different fractionation procedures that are ...
Suzanne Wahrle, Pritam Das, Andrew C. Nyborg, Chris McLendon, Mikio Shoji, Takeshi Kawarabayashi, Linda H. Younkin, Steven G. Younkin, Todd E. Golde   +8 more
doaj   +1 more source

A Novel NIR-FRET Biosensor for Reporting PS/γ-Secretase Activity in Live Cells

Sensors, 2020
Presenilin (PS)/γ-secretase plays a pivotal role in essential cellular events via proteolytic processing of transmembrane proteins that include APP and Notch receptors. However, how PS/γ-secretase activity is spatiotemporally regulated by other molecular
Mei CQ Houser, Steven S Hou, Florian Perrin, Yuliia Turchyna, Brian J Bacskai, Oksana Berezovska, Masato Maesako   +6 more
doaj   +1 more source

Cholestenoic acid, an endogenous cholesterol metabolite, is a potent γ-secretase modulator. [PDF]

, 2015
BackgroundAmyloid-β (Aβ) 42 has been implicated as the initiating molecule in the pathogenesis of Alzheimer's disease (AD); thus, therapeutic strategies that target Aβ42 are of great interest.
Akula, Rajender, Ba, Saritha, Ceballos-Diaz, Carolina, Felsenstein, Kevin M, Golde, Todd E, Hochhaus, Günther, Jung, Joo In, Koo, Edward H, Ladd, Thomas B, Park, Hyo-Jin, Price, Ashleigh R, Ran, Yong, Shapiro, Gideon, Smithson, Lisa A, Tang, Yufei   +14 more
core   +3 more sources

Functional γ-secretase complex assembly in Golgi/trans-Golgi network: interactions among presenilin, nicastrin, Aph1, Pen-2, and γ-secretase substrates

Neurobiology of Disease, 2003
γ-Secretase is a proteolytic complex whose substrates include Notch, β-amyloid precursor protein (APP), and several other type I transmembrane proteins. Presenilin (PS) and nicastrin are known components of this high-molecular-weight complex, and recent ...
Stephanie Baulac, Matthew J LaVoie, W.Taylor Kimberly, Jennifer Strahle, Michael S Wolfe, Dennis J Selkoe, Weiming Xia   +6 more
doaj   +1 more source

Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. [PDF]

, 2016
The beta amyloid (Aβ) and other aggregating proteins in the brain increase with age and are frequently found within neurons. The mechanistic relationship between intracellular amyloid, aging and neurodegeneration is not, however, well understood.
Currais, Antonio, Daugherty, Daniel, M Armando, Aaron, Maher, Pam, Quehenberger, Oswald, Schubert, David   +5 more
core   +2 more sources

Development of a High-Throughput Assay for Screening of γ-Secretase Inhibitor with Endogenous Human, Mouse or Drosophila γ-Secretase

Molecules, 2009
Selective lowering of amyloid-β levels with small-molecule γ-secretase inhibitors is a promising therapeutic approach for Alzheimer’s disease. In this work, we developed a high throughput assay for screening of γ-secretase inhibitors with endogenous γ ...
Lie-Feng Wang, Xin Xie, Ru Zhang
doaj   +1 more source