ArticleScientific reports2015
Insulin-degrading enzyme prevents α-synuclein fibril formation in a nonproteolytical manner.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial.JAMA neurology · 2019Trial
- Narrative Review "Dual Frontiers in Neurodegeneration: Pharmacological Synergies and Divergences in Parkinson's Disease and Type 2 Diabetes Mellitus".Cellular and molecular neurobiology · 2026Review
- Genetic and clinical investigation of insulin-degrading enzyme in Parkinson's disease within the Chinese Han population.Frontiers in neuroscience · 2026Article
- Insulin-degrading enzyme confers neuroprotection in Parkinson's disease by inhibiting the Hippo signaling pathway.Cell death & disease · 2025Article
- Decreased expression of insulin-degrading enzyme increases gluconeogenesis and glucose production in cultured hepatocytes administered with glucagon.Scientific reports · 2025Article
- Insulin-Degrading Enzyme Regulates mRNA Processing and May Interact with the CCR4-NOT Complex.Cells · 2025Article
- Associations Between Diabetes Mellitus and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Unraveling the Ties: Type 2 Diabetes and Parkinson's Disease - A Nano-Based Targeted Drug Delivery Approach.Current diabetes reviews · 2025Review
- Parkinson's disease and metabolic disorders, understanding their shared co-morbidity through the autonomic nervous system.Advances in genetics · 2025Review
- Metabolic Dysfunction in Parkinson's Disease: Unraveling the Glucose-Lipid Connection.Biomedicines · 2024Review
- Islet cell stress induced by insulin-degrading enzyme deficiency promotes regeneration and protection from autoimmune diabetes.iScience · 2024Article
- The Contribution of Type 2 Diabetes to Parkinson's Disease Aetiology.International journal of molecular sciences · 2024Review
- Insulin-degrading enzyme regulates insulin-directed cellular autoimmunity in murine type 1 diabetes.Frontiers in immunology · 2024Article
- Chemical catalysis by biological amyloids.Biochemical Society transactions · 2023Article
- The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.Biomolecules · 2023Review
- Article
- The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson's Disease Pathogenesis.Nutrients · 2023Review
- CHCHD2 p.Thr61Ile knock-in mice exhibit motor defects and neuropathological features of Parkinson's disease.Brain pathology (Zurich, Switzerland) · 2023Article
- The Relationships Among Metal Homeostasis, Mitochondria, and Locus Coeruleus in Psychiatric and Neurodegenerative Disorders: Potential Pathogenetic Mechanism and Therapeutic Implications.Cellular and molecular neurobiology · 2023Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The insulin-degrading enzyme (IDE) degrades amyloidogenic proteins such as Amyloid β (Αβ) and Islet Amyloid Polypeptide (IAPP), i.e. peptides associated with Alzheimer's disease and type 2 diabetes, respectively. In addition to the protease activity normally associated with IDE function an additional activity involving the formation of stable, irreversible complexes with both Αβ and α-synuclein, an amyloidogenic protein involved in Parkinson's disease, was recently proposed. Here, we have investigated the functional consequences of IDE-α-synuclein interactions in vitro. We demonstrate that IDE in a nonproteolytic manner and at sub-stoichiometric ratios efficiently inhibits α-synuclein fibril formation by binding to α-synuclein oligomers making them inert to amyloid formation. Moreover, we show that, within a defined range of α-synuclein concentrations, interaction with α-synuclein oligomers increases IDE's proteolytic activity on a fluorogenic substrate. We propose that the outcomes of IDE-α-synuclein interactions, i.e. protection against α-synuclein amyloid formation and stimulated IDE protease activity, may be protective in vivo.
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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.