Presenilin, Notch, and the genesis and treatment of Alzheimer's disease
- 25 September 2001
- journal article
- review article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 98 (20) , 11039-11041
- https://doi.org/10.1073/pnas.211352598
Abstract
Elucidation of the proteolytic processing of the amyloid β-protein precursor (APP) has revealed that one of the two proteases (γ-secretase) that cleave APP to release amyloid β-protein (Aβ) is likely to be presenilin. Presenilin also mediates the γ-secretase-like cleavage of Notch receptors to enable signaling by their cytoplasmic domains. Therefore, APP and Notch may be the first identified substrates of a unique intramembranous aspartyl protease that has presenilin as its active-site component. In view of the evidence for a central role of cerebral build-up of Aβ in the pathogenesis of Alzheimer's disease, this disorder appears to have arisen in the human population as a late-life consequence of the conservation of a critical developmental pathway.Keywords
This publication has 38 references indexed in Scilit:
- FAD Mutations in Presenilin-1 or Amyloid Precursor Protein Decrease the Efficacy of a γ-Secretase Inhibitor: Evidence for Direct Involvement of PS1 in the γ-Secretase Cleavage ComplexNeurobiology of Disease, 2000
- Regulated Intramembrane ProteolysisCell, 2000
- Identification of a Novel Aspartic Protease (Asp 2) as β-SecretaseMolecular and Cellular Neuroscience, 1999
- β-Secretase Cleavage of Alzheimer's Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACEScience, 1999
- Peptidomimetic Probes and Molecular Modeling Suggest That Alzheimer's γ-Secretase Is an Intramembrane-Cleaving Aspartyl ProteaseBiochemistry, 1999
- The cell biology of β-amyloid precursor protein and presenilin in Alzheimer's diseaseTrends in Cell Biology, 1998
- Presenilin 1 Regulates the Processing of β-Amyloid Precursor Protein C-Terminal Fragments and the Generation of Amyloid β-Protein in Endoplasmic Reticulum and GolgiBiochemistry, 1998
- Production of the Alzheimer Amyloid β Protein by Normal Proteolytic ProcessingScience, 1992
- Isolation and quantification of soluble Alzheimer's β-peptide from biological fluidsNature, 1992
- Amyloid β-peptide is produced by cultured cells during normal metabolismNature, 1992