Endogenous γ-Secretase Is Linked to Phagocytic Activity in Microglial Cells [PDF]
Sensorsγ-Secretase has primarily been studied in neurons, whereas increasing evidence highlights its importance in microglia. Previous research has shown that the pharmacological inhibition of γ-secretase impairs microglial phagocytic activity.
Emily Williams +6 more
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The γ-secretase complex: from structure to function [PDF]
Frontiers in Cellular Neuroscience, 2014 One of the most critical pathological features of Alzheimer’s disease (AD) is the accumulation of β-amyloid (Aβ) peptides that form extracellular senile plaques in the brain. Aβ is derived from β-amyloid precursor protein through sequential cleavage by β-
Xian eZhang +4 more
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Recording γ-secretase activity in living mouse brains [PDF]
eLifeγ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell ...
Steven S Hou +8 more
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Emerging structures and dynamic mechanisms of γ-secretase for Alzheimer’s disease [PDF]
Neural Regeneration Researchγ-Secretase, called “the proteasome of the membrane,” is a membrane-embedded protease complex that cleaves 150+ peptide substrates with central roles in biology and medicine, including amyloid precursor protein and the Notch family of cell-surface ...
Yinglong Miao, Michael S. Wolfe
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The manipulator behind “Scissors”: γ -secretase and its modulators in Alzheimer’s disease [PDF]
Frontiers in Aging NeuroscienceThe intramembrane aspartic protease, γ-secretase, is a heterotetrameric protein complex composed of four integral membrane proteins: presenilin (PSEN), nicastrin (NCT), Anterior pharynx defective-1 (APH-1), and presenilin enhancer 2 (PEN-2).
Gao Ning +10 more
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Charting γ-secretase substrates by explainable AI [PDF]
Nature CommunicationsProteases recognize substrates by decoding sequence information—an essential cellular process elusive when recognition motifs are absent. Here, we unravel this problem for γ-secretase, an intramembrane-cleaving protease associated with Alzheimer’s ...
Stephan Breimann +11 more
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Neurobiology of Disease, 2004 γ-Secretase is a high molecular weight protein complex composed of four subunits, namely, presenilin (PS; 1 or 2), nicastrin, anterior pharynx defective-1 (Aph-1; A or B), and presenilin enhancer-2 (Pen-2), and is responsible for the cleavage of a number
Sébastien S. Hébert +8 more
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Hair Cell Generation in Cochlear Culture Models Mediated by Novel γ-Secretase Inhibitors [PDF]
Frontiers in Cell and Developmental Biology, 2021 Sensorineural hearing loss is prevalent within society affecting the quality of life of 460 million worldwide. In the majority of cases, this is due to insult or degeneration of mechanosensory hair cells in the cochlea. In adult mammals, hair cell loss is irreversible as sensory cells are not replaced spontaneously.
Silvia T. Erni +25 more
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Alzheimer’s disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling [PDF]
Elife, 2023 Katarzyna Marta Zoltowska +15 more
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Correction: γ‑Secretase modulator resistance of an aggressive Alzheimer‑causing presenilin mutant can be overcome in the heterozygous patient state by a set of advanced compounds [PDF]
Alzheimers Res TherJohannes Trambauer +11 more
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