ArticleThe Journal of biological chemistry2022
The transmembrane domain of the amyloid precursor protein is required for antiamyloidogenic processing by α-secretase ADAM10.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Clustering hinders APP α-secretase processing in the plasma membrane.Biophysical journal · 2026Article
- Toward a Unified Framework in Molecular Neurobiology of Alzheimer's Disease: Revisiting the Pathophysiological Hypotheses.Molecular neurobiology · 2025Review
- Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol.Cell & bioscience · 2023Review
- Inducing prion protein shedding as a neuroprotective and regenerative approach in pathological conditions of the brain: from theory to facts.Neural regeneration research · 2023Review
- Article
- Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases.International journal of nanomedicine · 2023Review
- The role of ADAM10 in astrocytes: Implications for Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurotoxic amyloid β-peptides are thought to be a causative agent of Alzheimer's disease in humans. The production of amyloid β-peptides from amyloid precursor protein (APP) could be diminished by enhancing α-processing; however, the physical interactions between APP and α-secretases are not well understood. In this study, we employed super-resolution light microscopy to examine in cell-free plasma membranes the abundance and association of APP and α-secretases ADAM10 (a disintegrin and metalloproteinase) and ADAM17. We found that both secretase molecules localize similarly closely to APP (within ≤50 nm). However, when cross-linking APP with antibodies directed against the GFP tag of APP, in confocal microscopy, we observed that only ADAM10 coaggregated with APP. Furthermore, we mapped the involved protein domain by using APP variants with an exchanged transmembrane segment or lacking cytoplasmic/extracellular domains. We identified that the transmembrane domain of APP is required for association with α-secretases and, as analyzed by Western blot, for α-processing. We propose that the transmembrane domain of APP interacts either directly or indirectly with ADAM10, but not with ADAM17, explaining the dominant role of ADAM10 in α-processing of APP. Further understanding of this interaction may facilitate the development of a therapeutic strategy based on promoting APP cleavage by α-secretases.
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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.