ArticleThe Biochemical journal2000
Purified recombinant insulin-degrading enzyme degrades amyloid beta-protein but does not promote its oligomerization.
Article in The Biochemical journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 86 citations in OpenAlex.
- Transferrin-Conjugated Melittin-Loaded L-Arginine-Coated Iron Oxide Nanoparticles for Mitigating Beta-Amyloid Pathology of the 5XFAD Mouse Brain.International journal of molecular sciences · 2023Article
- Cellular response to β-amyloid neurotoxicity in Alzheimer's disease and implications in new therapeutics.Animal models and experimental medicine · 2023Review
- Controlled and Selective Photo-oxidation of Amyloid-β Fibrils by OligomericACS applied materials & interfaces · 2022Article
- Medium-Chain Length Fatty Acids Enhance Aβ Degradation by Affecting Insulin-Degrading Enzyme.Cells · 2021Article
- The Tragedy of Alzheimer's Disease: Towards Better Management via Resveratrol-Loaded Oral Bilosomes.Pharmaceutics · 2021Article
- Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes.Chemical reviews · 2021Review
- Galectin-3 promotes Aβ oligomerization and Aβ toxicity in a mouse model of Alzheimer's disease.Cell death and differentiation · 2020Article
- Regulation of Diabetes: a Therapeutic Strategy for Alzheimer's Disease?Journal of Korean medical science · 2019Review
- Insulin signaling inCommunications biology · 2019Article
- Protective effect of valproic acid in streptozotocin-induced sporadic Alzheimer's disease mouse model: possible involvement of the cholinergic system.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- The aqueous phase of Alzheimer's disease brain contains assemblies built from ∼4 and ∼7 kDa Aβ species.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2015Article
- Specific amyloid β clearance by a catalytic antibody construct.The Journal of biological chemistry · 2015Article
- Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer's disease: prophylactic and therapeutic applications.Molecular neurobiology · 2015Article
- Alzheimer's disease and type 2 diabetes: multiple mechanisms contribute to interactions.Current diabetes reports · 2014Review
- Identification and quantification of amyloid beta-related peptides in human plasma using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2014Article
- Expression of the plant viral protease NIa in the brain of a mouse model of Alzheimer's disease mitigates Aβ pathology and improves cognitive function.Experimental & molecular medicine · 2012Article
- 17β-Estradiol regulates insulin-degrading enzyme expression via an ERβ/PI3-K pathway in hippocampus: relevance to Alzheimer's prevention.Neurobiology of aging · 2011Article
- Overexpression of Insulin Degrading Enzyme could Greatly Contribute to Insulin Down-regulation Induced by Short-Term Swimming Exercise.Laboratory animal research · 2011Article
- Effect of Metal Chelators on γ-Secretase Indicates That Calcium and Magnesium Ions Facilitate Cleavage of Alzheimer Amyloid Precursor Substrate.International journal of Alzheimer's disease · 2010Article
- Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model.Molecular neurodegeneration · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Amyloid beta-protein (Abeta) has been implicated as an early and essential factor in the pathogenesis of Alzheimer's disease. Although its cellular production has been studied extensively, little is known about Abeta clearance. Recently, insulin-degrading enzyme (IDE), a 110-kDa metalloendopeptidase, was found to degrade both endogenously secreted and synthetic Abeta peptides. Surprisingly, IDE-mediated proteolysis of [(125)I]Abeta(1-40) in microglial cell-culture media was accompanied by the formation of (125)I-labelled peptides with higher apparent molecular masses, raising the possibility that the degradation products act as 'seeds' for Abeta oligomerization. To directly address the role of IDE in Abeta degradation and oligomerization, we investigated the action of purified recombinant wild-type and catalytically inactive IDEs. Our data demonstrate that (i) IDE alone is sufficient to cleave purified Abeta that is either unlabelled, iodinated or (35)S-labelled; (ii) the initial cleavage sites are His(14)-Gln(15), Phe(19)-Phe(20) and Phe(20)-Ala(21); and (iii) incubation of IDE with [(125)I]Abeta, but not with [(35)S]-Abeta, leads to the formation of slower migrating species on gels. Since iodination labels N-terminal fragments of Abeta, and (35)S labels C-terminal products, we analysed unlabelled synthetic fragments of Abeta and determined that only the N-terminal fragments migrate with anomalously high molecular mass. These results indicate that IDE alone is sufficient to degrade Abeta at specific sites, and that its degradation products do not promote oligomerization of the intact Abeta peptide.
Indexed as
Identifiers
11023838PMC1221388W2011187492What OpenQuestion holds
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.