ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Preferential Regulation of Γ-Secretase-Mediated Cleavage of APP by Ganglioside GM1 Reveals a Potential Therapeutic Target for Alzheimer's Disease.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Spatial lipidomics of the human brain: systematic review of current state and future perspectives.Molecular psychiatry · 2026Pooled it
- A comprehensive landscape of mechanical stress-mediated lipid metabolism in human cavernous fibroblasts.Communications biology · 2026Article
- Ganglioside sialylation modulates tau internalization and pathology spread.Molecular psychiatry · 2026Article
- Alzheimer's Disease: From Pathogenesis to Emerging Therapeutic Targets.Journal of clinical medicine · 2026Review
- Gangliosides in molecular interactions and cell regulation.The Journal of biological chemistry · 2026Review
- Soluble fermentable dietary fiber attenuates age-related cognitive impairment via neuroimmune and antioxidant modulation: evidence from multilevel analyses in populations and aging mouse models.Frontiers in immunology · 2026Article
- Glycosphingolipids in Dementia: Insights from Mass Spectrometry and Systems Biology Approaches.Biomedicines · 2025Review
- The emerging landscape of brain glycosylation: from molecular complexity to therapeutic potential.Experimental & molecular medicine · 2025Review
- The application of tissue engineering strategies for uterine regeneration.Materials today. Bio · 2025Review
- Microglial circDlg1 modulates neuroinflammation by blocking PDE4B ubiquitination-dependent degradation associated with Alzheimer's disease.Theranostics · 2025Article
- Identification of AS1842856 as a novel small-molecule GSK3α/β inhibitor against Tauopathy by accelerating GSK3α/β exocytosis.Aging cell · 2025Article
- Myelin Lipid Alterations in Neurodegenerative Diseases: Landscape and Pathogenic Implications.Antioxidants & redox signaling · 2024Review
- Nitric oxide facilitates the S-nitrosylation and deubiquitination of Notch1 protein to maintain cancer stem cells in human NSCLC.Journal of cellular and molecular medicine · 2024Article
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- Alpha-Synuclein and GM1 Ganglioside Co-Localize in Neuronal Cytosol Leading to Inverse Interaction-Relevance to Parkinson's Disease.International journal of molecular sciences · 2024Article
- Spatial Neurolipidomics at the Single Amyloid-β Plaque Level in Postmortem Human Alzheimer's Disease Brain.ACS chemical neuroscience · 2024Article
- Gangliosides as Therapeutic Targets for Neurodegenerative Diseases.Journal of lipids · 2024Review
- Preferential Regulation of Γ-Secretase-Mediated Cleavage of APP by Ganglioside GM1 Reveals a Potential Therapeutic Target for Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- γ-secretase targeting in Alzheimer's disease.Journal of Alzheimer's disease reportsReview
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
A hallmark of Alzheimer's disease (AD) is the senile plaque, which contains β-amyloid peptides (Aβ). Ganglioside GM1 is the most common brain ganglioside. However, the mechanism of GM1 in modulating Aβ processing is rarely known. Aβ levels are detected by using Immunohistochemistry (IHC) and enzyme-linked immune-sorbent assay (ELISA). Cryo-electron microscopy (Cryo-EM) is used to determine the structure of γ-secretase supplemented with GM1. The levels of the cleavage of amyloid precursor protein (APP)/Cadherin/Notch1 are detected using Western blot analysis. Y maze, object translocation, and Barnes maze are performed to evaluate cognitive functions. GM1 leads to conformational change of γ-secretase structure and specifically accelerates γ-secretase cleavage of APP without affecting other substrates including Notch1, potentially through its interaction with the N-terminal fragment of presenilin 1 (PS1). Reduction of GM1 levels decreases amyloid plaque deposition and improves cognitive dysfunction. This study reveals the mechanism of GM1 in Aβ generation and provides the evidence that decreasing GM1 levels represents a potential strategy in AD treatment. These results provide insights into the detailed mechanism of the effect of GM1 on PS1, representing a step toward the characterization of its novel role in the modulation of γ-secretase activity and the pathogenesis of 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.