γ-Secretase

γ-secretase is a multi-subunit internal protease that cleaves within the transmembrane domain of its substrates. It is an integral membrane protein and minimally consists of four proteins; presenilin, nicastrin, APH-1 and PEN-2. γ-secretase is involved in the processing of Notch.

Products
Background
Literature
Gene Data

Modulators

Cat No Product Name / Activity
4898 TC-E 5006
γ-secretase modulator; reduces Aβ42 levels

Inhibitors

Cat No Product Name / Activity
4283 Begacestat
γ-secretase inhibitor; lowers Aβ40 and Aβ42 levels
2870 BMS 299897
Potent γ-secretase inhibitor
2654 Compound W
γ-secretase inhibitor
2634 DAPT
γ-secretase inhibitor
4489 DBZ
γ-secretase inhibitor; inhibits Notch pathway
4495 Flurizan
γ-secretase inhibitor; lowers Aβ42 levels in vitro
2677 JLK 6
Inhibitor of γ-secretase-mediated βAPP processing
2627 L-685,458
Potent and selective γ-secretase inhibitor
4000 MRK 560
γ-secretase inhibitor; attenuates amyloid plaque deposition
5751 PF 3084014 hydrobromide
Potent γ-secretase inhibitor

Related Targets

    γ-secretase is a multi-subunit internal protease that cleaves within the transmembrane domain of its substrates. It is an integral membrane protein and minimally consists of four proteins; presenilin, nicastrin, APH-1 and PEN-2. Presenilin is an aspartic protease and the catalytic subunit of the complex.

    γ-secretase is involved in the processing of Notch. The Notch receptor is a single transmembrane spanning protein involved in angiogenesis and cell differentiation during embryonic and adult life. Upon ligand binding, the extracellular domain is cleaved by a metalloprotease named TACE. Following this initial cleavage, γ-secretase cleaves within the transmembrane domain of the remaining Notch protein, releasing the intracellular domain (Nβ) into the cytoplasm. Nβ moves to the nucleus where it upregulates transcription of target genes such as Hes1, Hey1 and Hey2. Deficient Notch signaling impairs developmental angiogenesis in the embryo and prevents wound healing in adult tissues.

    Literature for γ-Secretase

    Cancer

    Cancer Research Product Guide

    A collection of over 750 products for cancer research, the guide includes research tools for the study of:

    • Cancer Metabolism
    • Epigenetics in Cancer
    • Receptor Signaling
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    • Angiogenesis
    • Invasion and Metastasis
    Neurodegeneration

    Neurodegeneration Product Guide

    A collection of over 275 products for neurodegeneration research, the guide includes research tools for the study of:

    • Alzheimer's disease
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    Alzheimer's

    Alzheimer's Poster

    Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia, affecting approximately 47 million people worldwide. Updated in 2015, this poster summarizes the structural and functional changes observed in the progression of this neurodegenerative disease, as well as classic AD drug targets.

    γ-Secretase Gene Data

    Gene Species Gene Symbol Gene Accession No. Protein Accession No.
    Presenilin-1 Human PSEN1 NM_000021 P49768
    Mouse Psen1 NM_008943 P49769
    Rat Psen1 NM_019163 P97887
    Presenilin-2 Human PSEN2 NM_000447 P49810
    Mouse Psen2 NM_001128605 Q61144
    Rat Psen2 NM_031087 O88777
    Nicastrin Human NCSTN NM_015331 Q92542
    Mouse Ncstn NM_021607 P57716
    Rat Ncstn NM_174864 Q8CGU6
    APH1A Human APH1A NM_016022 Q96BI3
    Mouse Aph1a NM_146104 Q8BVF7
    Rat Aph1a NM_001014255 Q5PQQ3
    APH1B Human APH1B NM_031301 Q8WW43
    Mouse Aph1b NM_177583 Q8C7N7
    Rat Aph1b NM_001047090 Q0PY50
    PEN-2 Human PSENEN NM_172341 Q9NZ42
    Mouse Psenen NM_025498 Q9CQR7
    Rat Psenen NM_001008764 Q6QI68
    CD147 Human BSG NM_001728 P35613
    Mouse Bsg NM_009768 P18572