Results 51 to 60 of about 20,912 (233)

Nonspecificity of Binding of γ-Secretase Modulators to the Amyloid Precursor Protein [PDF]

Biochemistry, 2009
Evidence that certain gamma-secretase modulators (GSMs) target the 99-residue C-terminal domain (C99) of the amyloid precursor protein, a substrate of gamma-secretase, but not the protease complex itself has been presented [Kukar, T. L., et al. (2008) Nature 453, 925-929].
Andrew J, Beel, Paul, Barrett, Paul D, Schnier, Stephen A, Hitchcock, Dhanashri, Bagal, Charles R, Sanders, John B, Jordan   +6 more
openaire   +2 more sources

δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities

Translational Neurodegeneration, 2020
Mammalian asparagine endopeptidase (AEP) is a cysteine protease that cleaves its protein substrates on the C-terminal side of asparagine residues. Converging lines of evidence indicate that AEP may be involved in the pathogenesis of several neurological ...
Zhentao Zhang, Ye Tian, Keqiang Ye
doaj   +1 more source

Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration

Advanced Science, Volume 13, Issue 12, 27 February 2026.
Plasticity changes of molecular networks form a cellular learning process. Signaling network plasticity promotes cancer, metastasis, and drug resistance development. 55 plasticity‐related cancer drug targets are listed (20 having already approved drugs, 9 investigational drugs, and 26 being drug target candidates).
Márk Kerestély, István Narozsny, Levente Szarka, Daniel V. Veres, Peter Csermely, Dávid Keresztes   +5 more
wiley   +1 more source

Intracellular trafficking of the β-secretase and processing of amyloid precursor protein [PDF]

IUBMB Life, 2011
The main component of the amyloid plaques found in the brains of those with Alzheimer's disease (AD) is a polymerized form of the β-amyloid peptide (Aβ) and is considered to play a central role in the pathogenesis of this neurodegenerative disorder. Aβ is derived from the proteolytic processing of the amyloid precursor protein (APP).
Pei, Zhi, Pei Zhi Cheryl, Chia, Cheryl, Chia, Paul A, Gleeson   +3 more
openaire   +2 more sources

Exposure to lead and incidence of Alzheimer's disease and all‐cause dementia in the United States

Alzheimer's &Dementia, Volume 22, Issue 2, February 2026.
Abstract INTRODUCTION Growing evidence suggests lead exposure may increase dementia risk, but evidence from human studies is limited. We investigated prospective associations between lead exposure and incident Alzheimer's disease (AD) and all‐cause dementia in nationally‐representative US populations.
Xin Wang, Kelly M. Bakulski, Erika Walker, Bhramar Mukherjee, Hiroko Dodge, Roger L. Albin, Henry L. Paulson, Sung Kyun Park   +7 more
wiley   +1 more source

Astroglial mGlu3 receptors promote alpha-secretase-mediated amyloid precursor protein cleavage

Neuropharmacology, 2014
Amyloid precursor protein (APP) shedding yields the Alzheimer's disease (AD)-related peptide amyloid β (Aβ) through β- and γ-secretase cleavage. Alternatively, α-secretase cleavage generates a soluble and neuroprotective fragment (sAPPα) while precludes the production of Aβ.
Durand, Daniela Elizabeth, Carniglia, Lila, Beauquis, Juan, Caruso, Carla Mariana, Saravia, Flavia Eugenia, Lasaga, Mercedes Isabel   +5 more
openaire   +3 more sources

CRISPR Transcriptional Activation Analysis Unmasks an Occult γ-Secretase Processivity Defect in Familial Alzheimer’s Disease Skin Fibroblasts

Cell Reports, 2017
Summary: Mutations in presenilin (PSEN) 1 and 2, which encode components of the γ-secretase (GS) complex, cause familial Alzheimer’s disease (FAD). It is hypothesized that altered GS-mediated processing of the amyloid precursor protein (APP) to the Aβ42 ...
Keiichi Inoue, Luis M.A. Oliveira, Asa Abeliovich   +2 more
doaj   +1 more source

Role of cholesterol in substrate recognition by $$\gamma$$ γ -secretase

Scientific Reports, 2021
$$\gamma$$ γ -Secretase is an enzyme known to cleave multiple substrates within their transmembrane domains, with the amyloid precursor protein of Alzheimer’s Disease among the most prominent examples.
Łukasz Nierzwicki, Michał Olewniczak, Paweł Chodnicki, Jacek Czub   +3 more
doaj   +1 more source

APP‐mediated intracellular signaling rescues sleep impairment and blood–brain barrier leakage in Alzheimer's disease mouse model

Alzheimer's &Dementia, Volume 22, Issue 2, February 2026.
Abstract INTRODUCTION Amyloid beta peptide (Aβ) accumulation in the brain is an Alzheimer´s disease (AD) hallmark. Sleep disturbances hamper Aβ production and clearance, thereby exacerbating the Aβ burden. The mechanisms involved remain unclear. We reported that amyloid precursor protein (APP), the Aβ source, possesses intracellular signaling that ...
Clémentine Puech, Anjana Sadanand, Neil Coleman, Marilyn Ikhane, Mohammad Badran, Rong Wang, David Gozal, Angèle T. Parent   +7 more
wiley   +1 more source

Association of active γ-secretase complex with lipid rafts

Journal of Lipid Research, 2005
Cholesterol has been implicated in the pathogenesis of Alzheimer's disease (AD). Although the underlying mechanisms are not yet clear, several studies have provided evidence for the involvement of cholesterol-rich lipid rafts in the production of amyloid
Yasuomi Urano, Ikuo Hayashi, Noriko Isoo, Patrick C. Reid, Yoshikazu Shibasaki, Noriko Noguchi, Taisuke Tomita, Takeshi Iwatsubo, Takao Hamakubo, Tatsuhiko Kodama   +9 more
doaj   +1 more source