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Type of protein
Gamma secretase is a multi-subunit protease complex, an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within
Gamma_secretase
Family of proteolytic enzymes
processed by beta secretase and gamma secretase. The alpha-secretase pathway is the predominant APP processing pathway. Thus, alpha-secretase cleavage precludes
Alpha_secretase
Progressive neurodegenerative disease
and post-injury repair. In Alzheimer's disease, the enzymes gamma secretase and beta secretase act together in a proteolytic process that divides APP into
Alzheimer's_disease
Protein-coding gene in the species Homo sapiens
Gamma-secretase-activating protein, also known as Protein pigeon homolog (PION) is a protein that in humans is encoded by the GSAP gene. The human PION
Gamma-secretase-activating protein
Gamma-secretase-activating_protein
Protein gene product
of the gamma secretase complex along with the catalytic subunit presenilin and the regulatory subunits nicastrin and PEN-2. The gamma-secretase complex
APH-1
Investigational gamma-secretase modulator
Nivegacetor is an investigational gamma-secretase modulator being developed by Roche for the treatment of Alzheimer's disease. The compound is also known
Nivegacetor
Group of peptides
amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate
Amyloid_beta
Protein-coding gene in the species Homo sapiens
the PSEN1 gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation
Presenilin-1
Protein-coding gene in the species Homo sapiens
(presenilin enhancer 2), is a protein that is a regulatory component of the gamma secretase complex, a protease complex responsible for proteolysis of transmembrane
PEN-2
Family of related multi class transmembrane proteins
transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified
Presenilin
Type of enzyme
fragments.[citation needed] Sequential cleavage by beta-secretase 1 (BACE) and gamma-secretase (γ-secretase) produces the amyloid-beta peptide fragment that
Amyloid-beta precursor protein secretase
Amyloid-beta_precursor_protein_secretase
Chemical compound
RO4929097 (RG-4733) is a gamma secretase inhibitor being studied as an anti-cancer drug. Targeting gamma secretase inhibits NOTCH signaling, which is
RO4929097
Chemical compound
A.; Steiner, H.; Willem, M.; Bally-Cuif, L.; Haass, C. (2002). "A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic
DAPT_(chemical)
Chemical compound
medication used for the treatment of desmoid tumors. It is a selective gamma secretase inhibitor that is taken by mouth. Nirogacestat was approved for medical
Nirogacestat
Enzyme
transmembrane domain by γ-secretase releases the intracellular domain of APP and produces amyloid-β. Since gamma-secretase cleaves APP closer to the cell
Beta-secretase_1
Series of molecular signals
Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments". The Journal of Biological
Notch_signaling_pathway
Mammalian protein found in humans
Cleavage by gamma secretase within the membrane-spanning domain after beta-secretase cleavage generates the amyloid-beta fragment; gamma secretase is a large
Amyloid-beta precursor protein
Amyloid-beta_precursor_protein
Protein-coding gene
member of a heteromeric secretase complex and regulates the complex's gamma-secretase activity without affecting its epsilon-secretase activity. Mutations
TMED10
Alzheimer's disease developed before the age of 65
domain (NICD) and APP-CTfgamma: evidence for distinct intramembranous "gamma-secretase" activities". Neuromolecular Medicine. 1 (1): 43–54. doi:10.1385/NMM:1:1:43
Early-onset Alzheimer's disease
Early-onset_Alzheimer's_disease
endosomes, cleaved by beta-secretase (BACE), after which it moves back to the cell surface to be cleaved by gamma secretase thus releasing the Aβ peptide
Alzheimer's disease in the Hispanic/Latino population
Alzheimer's_disease_in_the_Hispanic/Latino_population
Cell surface receptor found in humans
into secreted proteins by the actions of the plasma membrane protein gamma secretase. ApoE may be the signalling ligand responsible for ApoER2's role in
Low-density lipoprotein receptor-related protein 8
Low-density_lipoprotein_receptor-related_protein_8
Organic compound containing the cyclic group >CN2
site. The discovery that caprolactam-type gamma-secretase inhibitors target the SPP subunit of the gamma-secretase, which has been implicated in Alzheimer's
Diazirine
Extracellular deposits of the amyloid beta protein
enzymes: first, by beta secretase (or β-amyloid cleaving enzyme (BACE)) outside the membrane, and second, by gamma secretase (γ-secretase), an enzyme complex
Amyloid_plaques
Intramembrane cellular enzymes
Aspartyl proteases: this group includes presenilin, the active subunit of gamma secretase and signal peptide peptidases (SPPs) and SPP-like proteases, which
Intramembrane_protease
Protein found in humans
gene. Nicastrin (abbreviated NCT) is a protein that is part of the gamma secretase protein complex, which is one of the proteases involved in processing
Nicastrin
Topics referred to by the same term
protein Hemoglobin subunit gamma-1; see HBG1 Hemoglobin subunit gamma-2; see HBG2 Gamma secretase Laminin, gamma 1 Laminin, gamma 2 This disambiguation page
Gamma_subunit
American geneticist (born 1958)
"gamma secretase modulators (GSM)". GSM's reverse the Abeta42:Abeta40 ratio and thereby prevent amyloid plaques. Notably, they do not inhibit gamma-secretase
Rudolph_E._Tanzi
Chemical compound
studies identified that a modified version of imatinib can bind to gamma-secretase activating protein (GSAP). GSAP selectively increases the production
Imatinib
Central nervous system disease
APP is cleaved into smaller fragments by enzymes such as gamma secretase and beta secretase. One of these fragments gives rise to fibrils of amyloid beta
Neurodegenerative_disease
Genetic disorder
therapy. Other methods being studied include the use of antioxidants, gamma secretase inhibition, adrenergic agonists, and memantine. Research is often carried
Down_syndrome
Protein-coding gene in the species Homo sapiens
multiple myeloma, on its own and in conjunction with the selective gamma secretase inhibitor nirogacestat. GRCh38: Ensembl release 89: ENSG00000048462
B-cell_maturation_antigen
Medical condition
staging systems as they do not metastasize. Nirogacestat, a selective gamma secretase inhibitor, was approved for medical use in the United States in November
Aggressive_fibromatosis
Medicinal chemist
Bioavailable gamma-Secretase Inhibitor". Queen’s University Belfast research portal. Retrieved 2026-09-09. "Safety and Tolerability of the γ-Secretase Inhibitor
John_E._Macor
Belgian molecular biologist
Wolfe, M. S.; Ray, W. J.; Goate, A. (1999). "A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain". Nature
Bart_De_Strooper
cholesterol controls the clustering of amyloid precursor protein with gamma secretase in GM1 lipid domains. High cholesterol induces APP hydrolysis and the
Cholesterol_signaling
Formation of myelin sheaths in the nervous system
BA (26 November 2008). "Distinct stages of myelination regulated by gamma-secretase and astrocytes in a rapidly myelinating CNS coculture system". Neuron
Myelination
Irish pharmaceutical company
included programs focused on small molecule inhibitors of beta-secretase and gamma secretase, enzymes whose actions are thought to affect the accumulation
Élan
risk gene products including the amyloid precursor protein (APP) and gamma-secretase, as well as the APOE receptors and GWAS risk loci take part in similar
Biochemistry of Alzheimer's disease
Biochemistry_of_Alzheimer's_disease
Topics referred to by the same term
Nuclear Compton Telescope, a balloon-borne gamma-ray detector Nicastrin, a protein component of the gamma secretase enzyme complex Nocturnal clitoral tumescence
NCT
First person diagnosed with Alzheimer's disease (1850–1906)
this paper, a mutation in the PSEN1 gene was found, which alters the gamma-secretase function and is known as a possible cause of early-onset Alzheimer's
Auguste_Deter
Dutch scientist
Bai, currently at UTSW, in his group solved the structure of human Gamma secretase in a collaboration with Shi Yigong. Since 2016, Scheres has worked
Sjors_Scheres
Auditory sensory receptor nerve cells
new cells. Several Notch signaling pathway inhibitors, including the gamma secretase inhibitor LY3056480, are being studied for their potential ability
Hair_cell
Family of transport proteins
Ingano LA, Carey BW, Pettingell WH, Kovacs DM (June 2005). "Presenilin/gamma-secretase-mediated cleavage of the voltage-gated sodium channel beta2-subunit
Voltage-gated_sodium_channel
Topics referred to by the same term
Cytoplasmic/C-terminal Domain, the smaller cleavage product of APP by gamma-secretase Australian Institute of Company Directors, an organisation supporting
AICD
American gene editing company
study, which features PBCAR269A in combination with nirogacestat, a gamma secretase inhibitor. In 2020, the FDA granted fast track designation to PBCAR269A
Precision_BioSciences
can be found as a 24 or 26 residues peptide, depending on which is gamma secretase's cleavage. The peptide which has 26 residues, presents the following
P3_peptide
British neuroscientist
18, 2019. De Strooper, B.; et al. (1999). "A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain". Nature
Alison_Goate
Cleaved form of B-cell maturation antigen
and antibody production. The membrane bound BCMA can be cleaved by gamma secretase, resulting in sBCMA, and released into the blood. Serum BCMA is found
Serum B-cell maturation antigen
Serum_B-cell_maturation_antigen
Begthel H, Cozijnsen M, Robine S, Winton DJ, Radtke F, Clevers H. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas
List of intestinal epithelial differentiation genes
List_of_intestinal_epithelial_differentiation_genes
Transmembrane protein allowing sodium ions in and out
Ingano LA, Carey BW, Pettingell WH, Kovacs DM (June 2005). "Presenilin/gamma-secretase-mediated cleavage of the voltage-gated sodium channel beta2-subunit
Sodium_channel
Protein-coding gene in the species Homo sapiens
PMID 7490080. Lee SF, Srinivasan B, Sephton CF, et al. (Aug 2011). "Gamma-secretase-regulated proteolysis of the Notch receptor by mitochondrial intermediate
MIPEP
Neurochemical indicators
(APP) by beta-secretase (β-secretase) and gamma-secretase (γ-secretase) produces various forms of amyloid beta (Aβ) peptides. Most β-secretase activity originates
Biomarkers of Alzheimer's disease
Biomarkers_of_Alzheimer's_disease
American physician (born 1943)
aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity". Nature. 398 (6727): 513–517. Bibcode:1999Natur.398..513W
Dennis_J._Selkoe
Protein-coding gene in the species Homo sapiens
caused by varying cleavages of APP by either beta secretase and gamma secretase or alpha secretase. The longer forms of APP are prone to aggregating and
RBFOX1
Medical condition
PMID 25098767. Clinical trial number NCT01154452 for "Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With
Epithelioid_sarcoma
Protein-coding gene in the species Homo sapiens
(2006). "Ubiquilin regulates presenilin endoproteolysis and modulates gamma-secretase components, Pen-2 and nicastrin". Biochem. J. 391 (Pt 3): 513–25. doi:10
UBQLN2
Protein-coding gene in the species Homo sapiens
are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins
Presenilin-2
Protein-coding gene in humans
cleavage, and the resulting C-terminal fragment is a substrate for gamma-secretase". The Journal of Biological Chemistry. 284 (4): 2296–2306. doi:10.1074/jbc
PMEL_(gene)
Protein family
PMID 16829952. S2CID 129089. Fluhrer R, Grammer G, Israel L, et al. (2006). "A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease
Signal_peptide_peptidase
Protein-coding gene in the species Homo sapiens
activity which liberates fatty acids from glycerolipids. PEDF enhances gamma-secretase activity, leading to the cleavage of the VEGF receptor 1 (VEGFR-1)
PEDF
Protein-coding gene in the species Homo sapiens
PΔE. The membrane tethered PΔE fragment is further cleaved by the gamma secretase complex to yield a membrane-released fragment, PIC, that can translocate
PTPRK
Protein-coding gene
"TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity". Nature. 440 (7088): 1208–12. Bibcode:2006Natur
TMED2
Protein-coding gene in the species Homo sapiens
PMID 16829952. S2CID 129089. Fluhrer R, Grammer G, Israel L, et al. (2006). "A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease
SPPL2A
Activation of a protein by exposure to its substrate
beta and gamma secretase to yield a 40-42 amino acid peptide responsible for amyloid plaques associated with Alzheimer's disease. The secretase enzymes
Substrate_presentation
Chemical compound
et al. (April 2010). "Disposition and metabolism of semagacestat, a {gamma}-secretase inhibitor, in humans". Drug Metabolism and Disposition. 38 (4): 554–65
Semagacestat
Protein-coding gene in the species Homo sapiens
Biervliet J, Horré K, Depboylu C, et al. (2008). "Deficiency of Aph1B/C-gamma-secretase disturbs Nrg1 cleavage and sensorimotor gating that can be reversed
Neuregulin_1
Mammalian protein found in humans
activity compared to controls, and the hyperactivity is blocked using a gamma-secretase inhibitor. These in vitro studies suggest that increasing Aβ concentrations
MTOR
Protein-coding gene in the species Homo sapiens
ligands, Delta1 and Jagged2, are substrates for presenilin-dependent "gamma-secretase" cleavage". J. Biol. Chem. 278 (10): 7751–4. doi:10.1074/jbc.C200711200
JAG2
Protein-coding gene in the species Homo sapiens
peptidase forms a homodimer that is labeled by an active site-directed gamma-secretase inhibitor". J Biol Chem. 279 (15): 15153–60. doi:10.1074/jbc.M309305200
HM13
Protein found in humans
Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments". J. Biol. Chem. 278 (36):
Delta-like_1
Australian neuropathologist (born 1947)
strategies for anti-Alzheimer's treatments that suppress the beta secretase and gamma secretase enzymes that cleave APP to form Aβ, or modify the interactions
Colin_L._Masters
Protein-coding gene in the species Homo sapiens
domain of PTPmu to release the shed extracellular fragment, then by the gamma secretase complex in the transmembrane domain to release the PTPmu intracellular
PTPRM
Protein-coding gene in the species Homo sapiens
091582298. PMC 33278. PMID 11331760. Gao Y, Pimplikar SW (2002). "The gamma -secretase-cleaved C-terminal fragment of amyloid precursor protein mediates signaling
APPBP2
Protein-coding gene in humans
Israel L, Condron MM, Haffner C, Friedmann E, et al. (August 2006). "A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease
SPPL2B
Precursor microRNA family
chemotherapy and (in T-ALL) may impact the effectiveness of therapeutic gamma-secretase inhibitors. Baraniskin and al. study show that miR-21, miR-19, and
Mir-19 microRNA precursor family
Mir-19_microRNA_precursor_family
Pharmaceutical compound
Gielen O, Jacobs K, Provost S, et al. (June 2021). "PSEN1-selective gamma-secretase inhibition in combination with kinase or XPO-1 inhibitors effectively
Eltanexor
Protein-coding gene in the species Homo sapiens
PMID 15489334. Kim DY, Ingano LA, Carey BW, et al. (2005). "Presenilin/gamma-secretase-mediated cleavage of the voltage-gated sodium channel beta2-subunit
SCN2B
Protein-coding gene in the species Homo sapiens
S2CID 30699151. Liu CX, Ranganathan S, Robinson S, Strickland DK (2007). "gamma-Secretase-mediated release of the low density lipoprotein receptor-related protein
LRP1B
Protein-coding gene in humans
PMID 16381901. Stoeck A, Shang L, Dempsey PJ (July 2010). "Sequential and gamma-secretase-dependent processing of the betacellulin precursor generates a palmitoylated
Betacellulin
Protein-coding gene in the species Homo sapiens
(2003). "Processing of beta-amyloid precursor-like protein-1 and -2 by gamma-secretase regulates transcription". J. Biol. Chem. 277 (46): 44195–201. doi:10
APLP1
Protein-coding gene in the species Homo sapiens
PMID 9169836. Roncarati R, Sestan N, Scheinfeld MH, et al. (2002). "The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds
NUMBL
Chemical compound
Lee FY, Shah JJ, Bertino JR, Rosenfeld J, et al. (December 2017). "Gamma Secretase Inhibition by BMS-906024 Enhances Efficacy of Paclitaxel in Lung Adenocarcinoma"
BMS-906024
Protein-coding gene in the species Homo sapiens
family of membrane proteins associated with presenilin expression and gamma-secretase function". FASEB J. 22 (3): 819–27. doi:10.1096/fj.07-9072com. PMID 17928364
ORMDL1
Proteins performing more than one function
metabolism Glucose signaling/cell death control Presenilin P. patens γ-secretase Cystoskeletal function Fungus Aconitase S. cerevisiae TCA cycle enzyme
Protein_moonlighting
Protein family
Furthermore, it was shown that Pcdhs are proteolytically processed by γ-secretase complex, which releases soluble intracellular fragments into the cytoplasm
Protocadherin
Protein-coding gene in the species Homo sapiens
S2CID 21977507. He X, Chang WP, Koelsch G, Tang J (Jul 2002). "Memapsin 2 (beta-secretase) cytosolic domain binds to the VHS domains of GGA1 and GGA2: implications
GGA2
Protein-coding gene in the species Homo sapiens
Chang Wan-Pin; Koelsch Gerald; Tang Jordan (July 2002). "Memapsin 2 (beta-secretase) cytosolic domain binds to the VHS domains of GGA1 and GGA2: implications
GGA1
Human disease
genes produce proteins that are all components of a complex called gamma- (γ-) secretase. This complex cuts apart (cleaves) many different proteins, which
Hidradenitis_suppurativa
Human chromosome
encoding enzyme beta-1,3-galactosyltransferase 5 BACE2: encoding enzyme beta-secretase 2 BACH1: encoding transcription factor transcription regulator protein
Chromosome_21
Chemical compound
cleavage of the β-amyloid precursor protein (βΑPP) through β- and γ- secretases. Like other pro-inflammatory mediators, Aβ42 induces inflammation through
Protectin_D1
Protein domain
ADAM-17 more effectively down-regulates the Notch pathway than that of γ-secretase in renal carcinoma". Journal of Experimental & Clinical Cancer Research
ADAM_(protein)
Class of enzymes
hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth
Proprotein_convertase
Protein-coding gene in humans
Sasagawa N, Ishiura S (2002). "A secreted form of human ADAM9 has an alpha-secretase activity for APP". Biochem. Biophys. Res. Commun. 293 (2): 800–5. Bibcode:2002BBRC
ADAM9
Protein-coding gene in the species Homo sapiens
encoded by the GGA3 gene. This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous
GGA3
Computer simulations to discover and understand chemical properties
contacts analysis as a new approach for pharmacophore modeling: beta-secretase 1 and check point kinase 1 as case studies". Journal of Computer-aided
Molecular_dynamics
Field of study
Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase". primary. Nature Medicine. 14 (7): 723–30. Bibcode:2008NatMe..14..723F
Epigenetics of neurodegenerative diseases
Epigenetics_of_neurodegenerative_diseases
and is possibly a "prime candidate to host alien life". 9 January A gamma secretase inhibitor previously experimented for treating Alzheimer's disease
2013_in_science
Protein
apparatus. The amyloidogenic pathway leads to APP processing by γ-secretases and β-secretases such as BACE1, resulting in production of the neurotoxic amyloid
SNX8
Journal of Experimental Medicine shows that blocking the enzyme beta-secretase (BACE1) in mice can substantially reduce the formation of plaques responsible
2018_in_science
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GAMMA SECRETASE
GAMMA SECRETASE
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GAMMA SECRETASE
GAMMA SECRETASE
GAMMA SECRETASE
GAMMA SECRETASE
GAMMA SECRETASE
GAMMA SECRETASE
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