Gamma secretase
Efficacy of SPI-1865, a novel gamma-secretase modulator, in multiple rodent models
... of gamma secretase inhibitors led to severe side effects, including an increased number of goblet cells in the intestine and decreased intrathymic differentiation and lymphocyte development ...inhibiting ...
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Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors
... Results: Delivery of htt cDNA into the mouse striatum using adeno-associated virus or into primary cortical neurons using lentivirus generated cpA and cpB, indicating that neurons in brain and in vitro can form these ...
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Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease
... capture gamma secretase from a partially purified cell extract, plus or minus co-incubation with increasing concentrations of reference or test gamma secretase inhibitors, was developed to ...
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Role of gamma-secretase in human umbilical-cord derived mesenchymal stem cell mediated suppression of NK cell cytotoxicity
... This project was aimed at elucidating the underlying molecular mechanisms of UC-MSC mediated immune- modulatory effects on freshly isolated, human NK cells without the presence of any NK cell activating cytokine like ...
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Original Article Gamma secretase inhibitor enhances sensitivity to doxorubicin in MDA-MB-231 cells
... Abstract: Deregulated expression of molecular of the Notch signaling pathway is observed in malignant tumor. Notch signaling pathway is activated by a series of catalytic cleavage of the Notch receptor by gamma ...
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Gamma-secretase inhibition combined with platinum compounds enhances cell death in a large subset of colorectal cancer cells
... Results: 63 CRC lines contained a fragment with approximately the size of the Notch1 intracellular domain (NICD), which is required for signalling. Subsequent analyses with an antibody that specifically recognises the ...
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Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575
... In vivo effect of LY-411575 on neuritic abnormalities It has been shown previously that neuritic processes in the vicinity of senile plaques are significantly more distorted, or "curvy", supporting the toxic ...
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Autophagy dysfunction upregulates beta-amyloid peptides via enhancing the activity of γ-secretase complex
... In the current study, both autophagy inhibitor and inducer increased the activity of α -, β -, and γ -secretases, and enhanced A β production. Moreover, autophagy inhibitor may more activate γ -secretase and ...
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Quantification of gamma-secretase modulation differentiates inhibitor compound selectivity between two substrates Notch and amyloid precursor protein
... Genetic and neuropathologic evidence suggests that Alzheimer's disease (AD) is caused partly by the overpro- duction and lack of clearance of the amyloid β peptide (Aβ) [1]. This Aβ peptide is generated by sequential ...
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Targeting γ-secretase in breast cancer
... used GSI from Calbiochem, Z-IL-CHO (GSI-XII), can also suppress the activity of proteasome at concentrations that show cytotoxicity in breast cancer cells (authors’ unpublished observation). Although it is unlikely that ...
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Gamma-secretase Inhibitor Prevents Proliferation and Migration of Ductus Arteriosus Smooth Muscle Cells through the Notch3-HES1/2/5 Pathway
... Patent ductus arteriosus (PDA) can cause morbidity and mortality in neonates. Vascular remodeling, characterized by proliferation and migration of smooth muscle cells (SMCs), is an essential process for postnatal DA ...
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Gamma secretase inhibitors of Notch signaling
... Abstract: The numerous processes involved in the etiology of breast cancer such as cell survival, metabolism, proliferation, differentiation, and angiogenesis are currently being elucidated. However, underlying ...
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Biological function of Presenilin and its role in AD pathogenesis
... (Asp 257 in transmemberane 6 (TM6) and Asp 385 in TM7) are located at NTF and CTF of presenilins, respectively. Mutations on either aspartate abolish the enzymatic activ- ity of γ-secretase complex [60]. With a ...
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QSAR STUDIES & DESIGNING OF POTENT HETEROCYCLIC COMPOUNDS AS γ SECRETASE INHIBITORS
... γ- secretase to release P3 or Aβ peptides, respectively. Since β-secretase and γ-secretase are responsible for the production of amyloid peptide (Aβ), which is believed to play a central role in the ...
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Literature review of Notch melanoma receptors
... by gamma-secretase complex and translocated to the nucleus where it binds to a transcriptional regulatory protein, the Jkappa protein (RBPJK) and its cofactor ...
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Cancer Stem Cells as a new promising approach of efficient oncological treatment - the review of literature
... that gamma secretase inhibitors impede Notch signaling pathway, which leads to a decrease of tumour markers expression and consequently decline in vivo tumour ...
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The miR-193a-3p-regulated ING5 gene activates the DNA damage response pathway and inhibits multi-chemoresistance in bladder cancer
... B, The mRNA levels qRT-PCR of ING5, a downstream target gene of the DNA damage, NF-κB and Myc/Max pathways and a component of the gamma-secretase complex in the miR-193a-3p mimicor ING5 [r] ...
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The role of MyD88 in embryonal carcinoma stem cells
... GSIs: Gamma Secretase Inhibitors hEC: Human Embryonal Carcinoma hES: Human Embryonic Stem cells HGF: Hepatocyte Growth Factor Hh: Hedgehog HMBA: Hexamethylene Bisacetamide HSC: Haematopo[r] ...
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Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application
... of gamma-secretase, has been tested in phase I study in refractory metastatic or locally advanced solid tumors [99], and phase II studies for metastatic melanoma [100], metastatic colorectal cancer [101] ...
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Notch pathway activation is essential for maintenance of stem-like cells in early tongue cancer
... by gamma secretase inhibitor or shRNA mediated knockdown of NOTCH1 inhibits spheroid forming capacity, transformation, survival and migration of the HNSCC cells suggesting an oncogenic role of NOTCH1 in ...
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