Cited by 178Alzheimer's disease research and treatmentsProtease and Inhibitor MechanismsPeptidase Inhibition and Analysis

Amyloid β-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin

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Malito, E., Hulse, R. E., Tang, W.-J.·2008·Cellular and Molecular Life Sciences

Abstract

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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  1. [1]Puente XS Sanchez LM Overall CM Lopez-Otin C 2003 Human and mouse proteases: a comparative genomic approach Nat Rev Genet 4 544 58 12838346
  2. [3]Im H Manolopoulou M Malito E Shen Y Zhao J Neant-Fery M Sun CY Meredith SC Sisodia SS Leissring MA Tang WJ 2007 Structure of substrate-free human insulin-degrading enzyme (IDE) and biophysical analysis of ATP-induced conformational switch of IDE J Biol Chem 282 25453 63 17613531
  3. [5]Oefner C D'Arcy A Hennig M Winkler FK Dale GE 2000 Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon J Mol Biol 296 341 9 10669592
  4. [9]Hartmann-Petersen R Gordon C 2004 Proteins interacting with the 26S proteasome Cell Mol Life Sci 61 1589 95 15224183 PMC11138787
  5. [21]Tanzi RE Moir RD Wagner SL 2004 Clearance of Alzheimer's Abeta peptide: the many roads to perdition Neuron 43 605 8 15339642
  6. [26]Rawlings ND Morton FR Barrett AJ 2006 MEROPS: the peptidase database Nucleic Acids Res 34 D270 2 16381862 PMC1347452
  7. [31]Selkoe DJ 2001 Clearing the brain's amyloid cobwebs Neuron 32 177 80 11683988
  8. [41]Taubes G 2003 Neuroscience. Insulin insults may spur Alzheimer's disease Science 301 40 1 12843374
  9. [43]Maskos K Messerschmidt A Dode W Cygler M 2004 Handbook of metalloproteins John Wiley &Sons 3 190 198
  10. [47]Mzhavia N Berman YL Qian Y Yan L Devi LA 1999 Cloning, expression, and characterization of human metalloprotease 1: a novel member of the pitrilysin family of metalloendoproteases DNA Cell Biol 18 369 80 10360838
  11. [49]Lustbader JW Cirilli M Lin C Xu HW Takuma K Wang N Caspersen C Chen X Pollak S Chaney M Trinchese F Liu S Gunn-Moore F Lue LF Walker DG Kuppusamy P Zewier ZL Arancio O Stern D Yan SS Wu H 2004 ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease Science 304 448 52 15087549
  12. [53]Turner AJ Tanzawa K 1997 Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX Faseb J 11 355 64 9141502
  13. [55]Eckman EA Reed DK Eckman CB 2001 Degradation of the Alzheimer's amyloid beta peptide by endothelin-converting enzyme J Biol Chem 276 24540 8 11337485
  14. [57]Iwata N Takaki Y Fukami S Tsubuki S Saido TC 2002 Region-specific reduction of A beta-degrading endopeptidase, neprilysin, in mouse hippocampus upon aging J Neurosci Res 70 493 500 12391610
  15. [94]Sticht H Bayer P Willbold D Dames S Hilbich C Beyreuther K Frank RW Rosch P 1995 Structure of amyloid A4-(1–40)-peptide of Alzheimer's disease Eur J Biochem 233 293 8 7588758

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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
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
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
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Health Sciences › Medicine › Oncology › 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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