ArticleBMC neuroscience2008
Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants.
Article in BMC neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Intracellular protein GBF1 displays significant associations with amyloid pathology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Delineating the Role of GxxxG Motif in Amyloidogenesis: A New Perspective in Targeting Amyloid-Beta Mediated AD Pathogenesis.ACS bio & med chem Au · 2024Review
- Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol.Cell & bioscience · 2023Review
- The Binding of Different Substrate Molecules at the Docking Site and the Active Site of γ-Secretase Can Trigger Toxic Events in Sporadic and Familial Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Formation of extramembraneProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates.Biomedicines · 2022Review
- Effect of Cholesterol on C99 Dimerization: Revealed by Molecular Dynamics Simulations.Frontiers in molecular biosciences · 2022Article
- Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease.iScience · 2021Article
- The dark side of Alzheimer's disease: unstructured biology of proteins from the amyloid cascade signaling pathway.Cellular and molecular life sciences : CMLS · 2020Article
- Bicelles Rich in both Sphingolipids and Cholesterol and Their Use in Studies of Membrane Proteins.Journal of the American Chemical Society · 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
- Coupled Transmembrane Substrate Docking and Helical Unwinding in Intramembrane Proteolysis of Amyloid Precursor Protein.Scientific reports · 2018Article
- Packing Density of the Amyloid Precursor Protein in the Cell Membrane.Biophysical journal · 2018Article
- β-Sheet Structure within the Extracellular Domain of C99 Regulates Amyloidogenic Processing.Scientific reports · 2017Article
- Dominant negative effect of the loss-of-function γ-secretase mutants on the wild-type enzyme through heterooligomerization.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Structural Characterization of the Amyloid Precursor Protein Transmembrane Domain and Its γ-Cleavage Site.ACS omega · 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
- The Metalloprotease Meprin β Is an Alternative β-Secretase of APP.Frontiers in molecular neuroscience · 2016Review
- Extension of a protein docking algorithm to membranes and applications to amyloid precursor protein dimerization.Proteins · 2015Article
- Analysis by a highly sensitive split luciferase assay of the regions involved in APP dimerization and its impact on processing.FEBS open bio · 2015Article
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Authors and funding
8 authors.
Funding
Abstract
backgroundAmyloid precursor protein (APP) is enzymatically cleaved by gamma-secretase to form two peptide products, either Abeta40 or the more neurotoxic Abeta42. The Abeta42/40 ratio is increased in many cases of familial Alzheimer's disease (FAD). The transmembrane domain (TM) of APP contains the known dimerization motif GXXXA. We have investigated the dimerization of both wild type and FAD mutant APP transmembrane domains.
resultsUsing synthetic peptides derived from the APP-TM domain, we show that this segment is capable of forming stable transmembrane dimers. A model of a dimeric APP-TM domain reveals a putative dimerization interface, and interestingly, majority of FAD mutations in APP are localized to this interface region. We find that FAD-APP mutations destabilize the APP-TM dimer and increase the population of APP peptide monomers.
conclusionThe dissociation constants are correlated to both the Abeta42/Abeta40 ratio and the mean age of disease onset in AD patients. We also show that these TM-peptides reduce Abeta production and Abeta42/Abeta40 ratios when added to HEK293 cells overexpressing the Swedish FAD mutation and gamma-secretase components, potentially revealing a new class of gamma-secretase inhibitors.
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