ArticleStructure (London, England : 1993)2014
Conformational changes induced by the A21G Flemish mutation in the amyloid precursor protein lead to increased Aβ production.
Article in Structure (London, England : 1993), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Distinct amyloid-β filament fold in individuals with APP Flemish mutation.Nature structural & molecular biology · 2026Article
- Therapeutic Options for Alzheimer's Disease and Aging-Associated Cognitive Decline: State of the Art in the ACH2.0 Paradigm.International journal of molecular sciences · 2026Review
- Transient cholesterol interactions with the amyloid precursor protein involved in Alzheimer's disease pathogenesis.Biophysical reviews · 2025Review
- Alzheimer's Is a Multiform Disease of Sustained Neuronal Integrated Stress Response Driven by the C99 Fragment Generated Independently of AβPP; Proteolytic Production of Aβ Is Suppressed in AD-Affected Neurons: Evolution of a Theory.International journal of molecular sciences · 2025Review
- Diverse Interactions of Sterols with Amyloid Precursor Protein Transmembrane Domain Can Shift Distribution Between Alternative Amyloid-β Production Cascades in Manner Dependent on Local Lipid Environment.International journal of molecular sciences · 2025Article
- Article
- Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations.The Biochemical journal · 2024Review
- Quintessential Synergy: Concurrent Transient Administration of Integrated Stress Response Inhibitors and BACE1 and/or BACE2 Activators as the Optimal Therapeutic Strategy for Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Delineating the Role of GxxxG Motif in Amyloidogenesis: A New Perspective in Targeting Amyloid-Beta Mediated AD Pathogenesis.ACS bio & med chem Au · 2024Review
- Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates.Biomedicines · 2022Review
- Insights into Cerebral Amyloid Angiopathy Type 1 and Type 2 from Comparisons of the Fibrillar Assembly and Stability of the Aβ40-Iowa and Aβ40-Dutch Peptides.Biochemistry · 2022Article
- Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer's Disease Development.Molecules (Basel, Switzerland) · 2021Review
- Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.Chemical reviews · 2021Review
- Anti-Parallel β-Hairpin Structure in Soluble Aβ Oligomers of Aβ40-Dutch and Aβ40-Iowa.International journal of molecular sciences · 2021Article
- Dimeric Transmembrane Orientations of APP/C99 Regulate γ-Secretase Processing Line Impacting Signaling and Oligomerization.iScience · 2020Article
- Copper stabilizes antiparallel β-sheet fibrils of the amyloid β40 (Aβ40)-Iowa variant.The Journal of biological chemistry · 2020Article
- Influence of the familial Alzheimer's disease-associated T43I mutation on the transmembrane structure and γ-secretase processing of the C99 peptide.The Journal of biological chemistry · 2019Article
- β-Sheet Structure within the Extracellular Domain of C99 Regulates Amyloidogenic Processing.Scientific reports · 2017Article
- Dimerization of the transmembrane domain of amyloid precursor protein is determined by residues around the γ-secretase cleavage sites.The Journal of biological chemistry · 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
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10 authors at 3 institutions in 2 countries.
Funding
Abstract
Proteolysis of the β C-terminal fragment (β-CTF) of the amyloid precursor protein generates the Aβ peptides associated with Alzheimer's disease. Familial mutations in the β-CTF, such as the A21G Flemish mutation, can increase Aβ secretion. We establish how the Flemish mutation alters the structure of C55, the first 55 residues of the β-CTF, using FTIR and solid-state NMR spectroscopy. We show that the A21G mutation reduces β sheet structure of C55 from Leu17 to Ala21, an inhibitory region near the site of the mutation, and increases α-helical structure from Gly25 to Gly29, in a region near the membrane surface and thought to interact with cholesterol. Cholesterol also increases Aβ peptide secretion, and we show that the incorporation of cholesterol into model membranes enhances the structural changes induced by the Flemish mutant, suggesting a common link between familial mutations and the cellular environment.
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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.