Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease [PDF]
Frontiers in Molecular Neuroscience, 2023 Recent clinical data with three therapeutic anti-Aβ antibodies have demonstrated that removal of Aβ-amyloid plaques in early Alzheimer's disease (AD) can attenuate disease progression.
Gunnar Nordvall +6 more
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Inhibition of gamma-secretase activity without interfering in Notch signalling decreases inflammatory response in patients with cutaneous leishmaniasis [PDF]
Emerging Microbes and Infections, 2021 Cutaneous leishmaniasis (CL) patients present an exacerbated inflammatory response associated with tissue damage and ulcer development. Increasing numbers of patients have exhibited treatment failure, which remains not well understood.
Maurício T. Nascimento +8 more
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Neurobiology of Disease, 2005 In Alzheimer's disease, the complex catabolism of amyloid precursor protein (APP) leads to the production of amyloid-beta (Abeta) peptide, the major component of amyloid deposits.
Valerie Vingtdeux +2 more
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Activity of the Gamma Secretase Inhibitor AL101 in Desmoid Tumors: A Case Report of 2 Adult Cases [PDF]
Current Oncology, 2021 Desmoid tumors (aggressive fibromatosis) are soft tissue mesenchymal tumors that can be locally invasive and life-threatening. Depending on the location, these tumors are often unresectable or tend to recur after surgery.
David Chan +3 more
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Sustained notch signaling inhibition with a gamma-secretase inhibitor prevents traumatic heterotopic ossification [PDF]
Journal of Orthopaedic Translation, 2023 Background: Traumatic heterotopic ossification (THO) is a devastating sequela following traumatic injuries and orthopedic surgeries. To date, the exact molecular mechanism of THO formation is still unclear, which hinders the development of effective ...
Zheng Wang +6 more
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Identification of presenilin mutations that have sufficient gamma-secretase proteolytic activity to mediate Notch signaling but disrupt organelle and neuronal health [PDF]
Neurobiology of DiseaseMutations that cause familial Alzheimer's disease (AD) are predominantly found in the presenilin (PSEN) encoding genes PSEN1 and PSEN2. While the association of PSEN mutations with familial AD have been known for over 20 years, the mechanism underlying ...
Zahra Ashkavand +5 more
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PSEN1-selective gamma-secretase inhibition in combination with kinase or XPO-1 inhibitors effectively targets T cell acute lymphoblastic leukemia [PDF]
Journal of Hematology & Oncology, 2021 Background T cell acute lymphoblastic leukemia (T-ALL) is a high-risk subtype that comprises 10–15% of childhood and 20–25% of adult ALL cases. Over 70% of T-ALL patients harbor activating mutations in the NOTCH1 signaling pathway and are predicted to be
Inge Govaerts +11 more
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Pharmacology of nivegacetor (RG6289), a potent and selective gamma secretase modulator in clinical development for the treatment of Alzheimer’s disease [PDF]
Frontiers in PharmacologyBackgroundAlzheimer’s Disease (AD) is a prevalent neurodegenerative disorder which involves a complex pathobiology driven by amyloid-beta (Aβ) and tau pathologies, among other factors.
Lothar Lindemann +15 more
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Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury [PDF]
Frontiers in Cell and Developmental Biology, 2020 In a recent study, we showed that GABA and baclofen (a GABAB receptor agonist) inhibit caspase activation and promote axon regeneration in descending neurons of the sea lamprey brainstem after a complete spinal cord injury (Romaus-Sanjurjo et al., 2018a).
Daniel Sobrido-Cameán +6 more
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Targeting γ-secretase in breast cancer
Breast Cancer: Targets and Therapy, 2012 Jianxun Han,1 Qiang Shen21Department of Chemical Engineering and Applied Chemistry, University of Toronto, 2Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, Toronto, Ontario, CanadaAbstract ...
Han J, Shen Q
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