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Amyloid β-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin
Open accessAbstract
The accumulation of aggregates of amyloidogenic peptides is associated with numerous human diseases. One well studied example is the association between deposition of amyloid beta (Abeta) and Alzheimer's disease. Insulin degrading enzyme and neprilysin are involved in the clearance of Abeta, and presequence peptidase is suggested to play a role in the degradation of mitochondrial Abeta. Recent structural analyses reveal that these three peptidases contain a catalytic chamber (crypt) that selectively encapsulates and cleaves amyloidogenic peptides, hence the name cryptidase. The substrate selectivity of these cryptidases is determined by the size and charge distribution of their crypt as well as the conformational flexibility of substrates. The interaction of Abeta with the catalytic core of these cryptidases is controlled by conformational changes that make the catalytic chambers accessible for Abeta binding. These new structural and biochemical insights into cryptidases provide potential therapeutic strategies for the control of Abeta clearance.
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“The decreased plaque deposition was also related to increased levels of the proteolytic enzyme insulin-degrading enzyme (IDE) [77], previously reported to degrade Aβ [83].”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [83]
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Metadata
- Authors
- Malito, E., Hulse, R. E., & Tang, W.-J.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Tang, W.-J.
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2008-05-13
- Volume
- 65
- Issue
- 16
- Pages
- 2574-2585
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC2756532
- OpenAlex
- W2007899228
- Cited by
- 176
- References
- 89
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 5 · 2023: 14 · 2022: 8 · 2021: 9 · 2020: 5 · 2019: 6 · 2018: 12 · 2017: 7 · 2016: 9 · 2015: 17 · 2014: 12 · 2013: 12 · 2012: 6
- FWCI
- 8.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01 GM81539, T32GM007839, R01GM081539, T32GM07839)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Peptidase Inhibition and Analysis
- Keywords
- amyloid-beta, insulin-degrading enzyme, neprilysin, amyloid-beta clearance, Alzheimer's disease, substrate specificity, conformational flexibility, peptide aggregation
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Animals, Humans, Insulysin, Molecular Sequence Data, Protein Processing, Post-Translational, Substrate Specificity, Neprilysin, Amyloid beta-Peptides
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