ArticleCell reports2021
Axonal generation of amyloid-β from palmitoylated APP in mitochondria-associated endoplasmic reticulum membranes.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 67 citations in OpenAlex.
- Inter-Organelle Membrane Contact Sites as Physiological Regulatory Hubs in the Brain: From Neurons to Glial Cells.Biomolecules · 2026Review
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
- Alzheimer's disease: disrupted communication between the endoplasmic reticulum and mitochondria.Journal of neurology · 2026Review
- Variecolactone, a Natural PDE4 Inhibitor from Marine-DerivedBiomolecules · 2026Article
- Amyloid precursor protein interacts with the mitochondrial phosphatase PGAM5 and regulates mitochondrial respiration.bioRxiv : the preprint server for biology · 2026Article
- Dual sigma receptor 1 and 2 modulator improves memory behavior in mouse model of age-related cognitive decline.The Journal of pharmacology and experimental therapeutics · 2026Article
- Article
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- Calcium signaling hypothesis: A non-negligible pathogenesis in Alzheimer's disease.Journal of advanced research · 2025Review
- On The Retrograde Transport of RNA-Loaded Lipid Nanoparticles Designed for Brain Delivery.ACS nanoscience Au · 2025Article
- Review
- Amyloid-β protein precursor modulates mitophagy and mitochondrial function through its cellular localization.Journal of Alzheimer's disease : JAD · 2025Article
- The complex web of membrane contact sites in brain aging and neurodegeneration.Cellular and molecular life sciences : CMLS · 2025Review
- Review
- The impact of ERCell death & disease · 2025Article
- Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.Biomedicines · 2025Review
- Development of Carbon-11 Labeled Pyrimidine Derivatives as Novel Positron Emission Tomography (PET) Agents Enabling Brain Sigma-1 Receptor Imaging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Visual Analysis of Research Hotspots and Trends on Mitochondria-Associated Membranes in the Past 20 Years-Focused on Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Phosphatidate phosphatase Lipin1 alters mitochondria-associated endoplasmic reticulum membranes (MAMs) homeostasis: effects which contribute to the development of diabetic encephalopathy.Journal of neuroinflammation · 2025Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Axonal generation of Alzheimer's disease (AD)-associated amyloid-β (Aβ) plays a key role in AD neuropathology, but the cellular mechanisms involved in its release have remained elusive. We previously reported that palmitoylated APP (palAPP) partitions to lipid rafts where it serves as a preferred substrate for β-secretase. Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are cholesterol-rich lipid rafts that are upregulated in AD. Here, we show that downregulating MAM assembly by either RNA silencing or pharmacological modulation of the MAM-resident sigma1 receptor (S1R) leads to attenuated β-secretase cleavage of palAPP. Upregulation of MAMs promotes trafficking of palAPP to the cell surface, β-secretase cleavage, and Aβ generation. We develop a microfluidic device and use it to show that MAM levels alter Aβ generation specifically in neuronal processes and axons, but not in cell bodies. These data suggest therapeutic strategies for reducing axonal release of Aβ and attenuating β-amyloid pathology in AD.
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Registered trials
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.