ArticleNeurobiology of disease2008
Aggregation and catabolism of disease-associated intra-Abeta mutations: reduced proteolysis of AbetaA21G by neprilysin.
Article in Neurobiology of disease, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 84 citations in OpenAlex.
- The effect of LCZ696 (sacubitril/valsartan) on amyloid-β concentrations in cerebrospinal fluid in healthy subjects.British journal of clinical pharmacology · 2016Trial
- Distinct amyloid-β filament fold in individuals with APP Flemish mutation.Nature structural & molecular biology · 2026Article
- Brain Hydrophobic Peptides Antagonists of Neurotoxic Amyloid β Peptide Monomers/Oligomers-Protein Interactions.International journal of molecular sciences · 2023Review
- Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration.Aging cell · 2022Review
- Macrocyclic Peptides Derived from Familial Alzheimer's Disease Mutants Show Charge-Dependent Oligomeric Assembly and Toxicity.ACS chemical neuroscience · 2022Article
- Influence of denaturants on amyloid β42 aggregation kinetics.Frontiers in neuroscience · 2022Article
- The Luminescent Conjugated Oligothiophene h-FTAA Attenuates the Toxicity of Different Aβ Species.Biochemistry · 2021Article
- Pulsed Hydrogen-Deuterium Exchange Reveals Altered Structures and Mechanisms in the Aggregation of Familial Alzheimer's Disease Mutants.ACS chemical neuroscience · 2021Article
- PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins.Acta neuropathologica · 2020Article
- Anomalous Salt Dependence Reveals an Interplay of Attractive and Repulsive Electrostatic Interactions in α-synuclein Fibril Formation.QRB discovery · 2020Article
- A method of predicting the in vitro fibril formation propensity of Aβ40 mutants based on their inclusion body levels in E. coli.Scientific reports · 2019Article
- On the role of sidechain size and charge in the aggregation of AProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Insights into the Molecular Mechanisms of Alzheimer's and Parkinson's Diseases with Molecular Simulations: Understanding the Roles of Artificial and Pathological Missense Mutations in Intrinsically Disordered Proteins Related to Pathology.International journal of molecular sciences · 2018Review
- β-Sheet Structure within the Extracellular Domain of C99 Regulates Amyloidogenic Processing.Scientific reports · 2017Article
- Human Brain-Derived Aβ Oligomers Bind to Synapses and Disrupt Synaptic Activity in a Manner That Requires APP.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Modulation of electrostatic interactions to reveal a reaction network unifying the aggregation behaviour of the Aβ42 peptide and its variants.Chemical science · 2017Article
- Familial Alzheimer's Disease Mutations within the Amyloid Precursor Protein Alter the Aggregation and Conformation of the Amyloid-β Peptide.The Journal of biological chemistry · 2017Article
- The Aggregation Paths and Products of Aβ42 Dimers Are Distinct from Those of the Aβ42 Monomer.Biochemistry · 2016Article
- Structural Polymorphism of Alzheimer's β-Amyloid Fibrils as Controlled by an E22 Switch: A Solid-State NMR Study.Journal of the American Chemical Society · 2016Article
- Real-Time Monitoring of Alzheimer's-Related Amyloid Aggregation via Probe Enhancement-Fluorescence Correlation Spectroscopy.ACS chemical neuroscience · 2015Article
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
Five point mutations within the amyloid beta-protein (Abeta) sequence of the APP gene are associated with hereditary diseases which are similar or identical to Alzheimer's disease and encode: the A21G (Flemish), E22G (Arctic), E22K (Italian), E22Q (Dutch) and the D23N (Iowa) amino acid substitutions. Although a substantial body of data exists on the effects of these mutations on Abeta production, whether or not intra-Abeta mutations alter degradation and how this relates to their aggregation state remain unclear. Here we report that the E22G, E22Q and the D23N substitutions significantly increase fibril nucleation and extension, whereas the E22K substitution exhibits only an increased rate of extension and the A21G substitution actually causes a decrease in the extension rate. These substantial differences in aggregation together with our observation that aggregated wild type Abeta(1-40) was much less well degraded than monomeric wild type Abeta(1-40), prompted us to assess whether or not disease-associated intra-Abeta mutations alter proteolysis independent of their effects on aggregation. Neprilysin (NEP), insulin degrading enzyme (IDE) and plasmin play a major role in Abeta catabolism, therefore we compared the ability of these enzymes to degrade wild type and mutant monomeric Abeta peptides. Experiments investigating proteolysis revealed that all monomeric peptides are degraded similarly by IDE and plasmin, but that the Flemish peptide was degraded significantly more slowly by NEP than wild type Abeta or any of the other mutant peptides. This finding suggests that resistance to NEP-mediated proteolysis may underlie the pathogenicity associated with the A21G mutation.
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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.