ReviewJournal of Alzheimer's disease : JAD2009
Gamma-secretase catalyzes sequential cleavages of the AbetaPP transmembrane domain.
Review in Journal of Alzheimer's disease : JAD, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 76 citations in OpenAlex.
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- Adverse Effects of AβBiomolecules · 2024Article
- Multiple Roles of Apolipoprotein E4 in Oxidative Lipid Metabolism and Ferroptosis During the Pathogenesis of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2024Review
- EPR Studies of Aβ42 Oligomers Indicate a Parallel In-Register β-Sheet Structure.ACS chemical neuroscience · 2024Article
- Lipid environment modulates processivity and kinetics of a presenilin homolog acting on multiple substrates in vitro.The Journal of biological chemistry · 2023Article
- The Labyrinthine Landscape of APP Processing: State of the Art and Possible Novel Soluble APP-Related Molecular Players in Traumatic Brain Injury and Neurodegeneration.International journal of molecular sciences · 2023Article
- Amyloidogenesis: What Do We Know So Far?International journal of molecular sciences · 2022Review
- The emerging role of furin in neurodegenerative and neuropsychiatric diseases.Translational neurodegeneration · 2022Review
- γ-Secretase in Alzheimer's disease.Experimental & molecular medicine · 2022Review
- Revisiting APP secretases: an overview on the holistic effects of retinoic acid receptor stimulation in APP processing.Cellular and molecular life sciences : CMLS · 2022Review
- The transmembrane amyloid precursor C99 protein exhibits non-specific interaction with tau.Biochemical and biophysical research communications · 2021Article
- APPsα rescues impaired CaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders.Frontiers in aging neuroscience · 2021Review
- Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer's Disease Mice, Independent of Amyloid-β Pathology.Journal of Alzheimer's disease reports · 2020Article
- Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a Cells.Molecules (Basel, Switzerland) · 2020Article
- Current status and future prospects of stem cell therapy in Alzheimer's disease.Neural regeneration research · 2020Article
- Amyloid Beta-Peptide Increases BACE1 Translation through the Phosphorylation of the Eukaryotic Initiation Factor-2Oxidative medicine and cellular longevity · 2020Article
- Conformational Dynamics of Transmembrane Domain 3 of Presenilin 1 Is Associated with the Trimming Activity of γ-Secretase.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
The biogenesis of the amyloid-beta peptide (Abeta) is a central issue in Alzheimer's disease (AD) research. Abeta is produced by beta- and gamma-secretases from the amyloid-beta protein precursor (AbetaPP). These proteases are targets for the development of therapeutic compounds to downregulate Abeta production. gamma-secretase has received more attention 1) because it generates the C-terminus of Abeta, which is important in the pathogenesis of AD because the longer Abeta species are more amyloidogenic, and 2) because it cleaves AbetaPP within its transmembrane domain. In the understanding the mechanism of gamma-secretase cleavage, three major cleavage sites have been identified, namely, gamma-cleavage site at Abeta(40/42), zeta-cleavage site at Abeta(46), and epsilon-cleavage site at Abeta(49). Moreover, the novel finding that some of the known gamma-secretase inhibitors inhibit the formation of secreted Abeta(40) and Abeta(42), but cause an intracellular accumulation of long Abeta(46), provided information extremely important for the development of strategies aimed at the design of gamma-secretase inhibitors to prevent and treat AD. In addition, it has been established that the C-terminus of Abeta is generated by a series of sequential cleavages: first, epsilon-cleavage, followed by zeta-cleavage and finally by gamma-cleavage, commencing from the membrane boundary to the middle of the AbetaPP membrane domain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.