ArticleScience translational medicine2021
GDE2-RECK controls ADAM10 α-secretase-mediated cleavage of amyloid precursor protein.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Genome-Wide CRISPR Screening Identifies Genetic Modulators of Amyloid Precursor Protein Processing.International journal of molecular sciences · 2026Article
- The Roles of the Membrane-Anchored Glycoprotein RECK in Animal Development, Tumor Suppression, and Beyond.Life (Basel, Switzerland) · 2026Review
- Regulation of glypican 6-mediated Wnt activation maintains TDP-43 nuclear localization in neurons.Scientific reports · 2025Article
- Regulation of Glypican 6-mediated Wnt activation maintains TDP-43 nuclear localization in neurons.bioRxiv : the preprint server for biology · 2025Article
- GALM Alleviates Aβ Pathology and Cognitive Deficit Through Increasing ADAM10 Maturation in a Mouse Model of Alzheimer's Disease.Neuroscience bulletin · 2025Article
- Circulating Biomarkers for the Early Diagnosis of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Novel Roles of the GPI-Anchor Cleaving Enzyme, GDE2, in Hippocampal Synaptic Morphology and Function.eNeuro · 2025Article
- RECK as a Potential Crucial Molecule for the Targeted Treatment of Sepsis.Journal of inflammation research · 2025Review
- PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT.Cancer research · 2024Article
- RECK/GPR124-driven WNT signaling in pancreatic and gastric cancer cells.Cancer science · 2024Article
- Article
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- Physiological regulation of neuronal Wnt activity is essential for TDP-43 localization and function.The EMBO journal · 2024Article
- MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway.International journal of molecular sciences · 2024Article
- Loss of GDE2 leads to complex behavioral changes including memory impairment.Behavioral and brain functions : BBF · 2024Article
- Evoked Weibel-Palade Body Exocytosis Modifies the Endothelial Cell Surface by Releasing a Substrate-Selective Phosphodiesterase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- ADAM10-a "multitasker" in sepsis: focus on its posttranslational target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- GDE6 promotes progenitor identity in the vertebrate neural tube.Frontiers in neuroscience · 2023Article
- Amyloid Cascade Hypothesis for the Treatment of Alzheimer's Disease: Progress and Challenges.Aging and disease · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
A disintegrin and metalloprotease 10 (ADAM10) is the α-secretase for amyloid precursor protein (APP). ADAM10 cleaves APP to generate neuroprotective soluble APPα (sAPPα), which precludes the generation of Aβ, a defining feature of Alzheimer's disease (AD) pathophysiology. Reduced ADAM10 activity is implicated in AD, but the mechanisms mediating ADAM10 modulation are unclear. We find that the plasma membrane enzyme glycerophosphodiester phosphodiesterase 2 (GDE2) stimulates ADAM10 APP cleavage by shedding and inactivating reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a glycosylphosphatidylinositol (GPI)-anchored inhibitor of ADAM10. In AD, membrane-tethered RECK is highly elevated and GDE2 is abnormally sequestered inside neurons. Genetic ablation of GDE2 phenocopies increased membrane RECK in AD, which is causal for reduced sAPPα, increased Aβ, and synaptic protein loss. RECK reduction restores the balance of APP processing and rescues synaptic protein deficits. These studies identify GDE2 control of RECK surface activity as essential for ADAM10 α-secretase function and physiological APP processing. Moreover, our results suggest the involvement of the GDE2-RECK-ADAM10 pathway in AD pathophysiology and highlight RECK as a potential target for therapeutic development.
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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.