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Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo
Although extensive data support a central pathogenic role for amyloid β protein (Aβ) in Alzheimer's disease, the amyloid hypothesis remains controversial, in part because a specific neurotoxicExpand
Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity
Accumulation of the amyloid-β protein (Aβ) in the cerebral cortex is an early and invariant event in the pathogenesis of Alzheimer's disease. The final step in the generation of Aβ from the β-amyloidExpand
c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma.
Human acute T-cell lymphoblastic leukemias and lymphomas (T-ALL) are commonly associated with gain-of-function mutations in Notch1 that contribute to T-ALL induction and maintenance. Starting from anExpand
A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain
Signalling through the receptor protein Notch, which is involved in crucial cell-fate decisions during development, requires ligand-induced cleavage of Notch. This cleavage occurs within theExpand
γ-Secretase is a membrane protein complex comprised of presenilin, nicastrin, aph-1, and pen-2
γ-Secretase catalyzes the intramembrane proteolysis of Notch, β-amyloid precursor protein, and other substrates as part of a new signaling paradigm and as a key step in the pathogenesis ofExpand
Presenilin: Running with Scissors in the Membrane
The presenilin-containing gamma-secretase complex is an unusual membrane-embedded protease that processes a wide variety of integral membrane proteins, clearing protein stubs from the lipid bilayerExpand
Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis.
Notch signaling regulates cell fate decisions in a wide variety of adult and embryonic tissues. Here we show that Notch pathway components and Notch target genes are upregulated in invasiveExpand
The surface of articular cartilage contains a progenitor cell population
It is becoming increasingly apparent that articular cartilage growth is achieved by apposition from the articular surface. For such a mechanism to occur, a population of stem/progenitor cells mustExpand
Growth Suppression of Pre-T Acute Lymphoblastic Leukemia Cells by Inhibition of Notch Signaling
ABSTRACT Constitutive NOTCH signaling in lymphoid progenitors promotes the development of immature T-cell lymphoblastic neoplasms (T-ALLs). Although it is clear that Notch signaling can initiateExpand
Presenilins and γ-secretase: structure, function, and role in Alzheimer Disease.
Presenilins were first discovered as sites of missense mutations responsible for early-onset Alzheimer disease (AD). The encoded multipass membrane proteins were subsequently found to be theExpand
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