ArticleStem cell reports2023
Pharmacologic enhancement of retromer rescues endosomal pathology induced by defects in the Alzheimer's gene SORL1.
Article in Stem cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The Alzheimer's disease risk gene SORL1 is a regulator of excitatory neuronal function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- SORL1 variant links endosomal amyloid precursor protein mis-sorting to axonal transport defects and neuronal dysfunction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- SORLA up-regulation suppresses pathological effects in aged tauopathy mouse brain.Science advances · 2026Article
- Estradiol ameliorates AD pathology and cognitive deficits by SORLA-mediated APP endosomal trafficking.Alzheimer's research & therapy · 2026Article
- RhoGEF12 regulates endosomal SORL1-retromer and its inhibition is therapeutic in human neuronal models of Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- TDP-43-mediated alternative polyadenylation is associated with a reduction in VPS35 and VPS29 expression in frontotemporal dementia.PLoS biology · 2026Article
- Stabilizing the retromer complex rescues synaptic dysfunction and endosomal trafficking deficits in an Alzheimer's disease mouse model.Acta neuropathologica communications · 2025Article
- Article
- EHBP1 suppresses liver fibrosis in metabolic dysfunction-associated steatohepatitis.Cell metabolism · 2025Article
- Article
- Therapeutic Potential of TPT-260 in Ischemic Stroke: An Investigation Into Its Anti-Inflammatory Effects and Impact on Microglial Activation.Journal of inflammation research · 2025Article
- Direct and indirect role of non-coding RNAs in company with amyloid and tau protein in promoting neuroinflammation in post-ischemic brain neurodegeneration.Frontiers in cellular neuroscience · 2025Review
- Therapeutic and preventive strategies based on the maladaptive plasticity hypothesis for Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- Haploinsufficiency and Alzheimer's Disease: The Possible Pathogenic and Protective Genetic Factors.International journal of molecular sciences · 2024Review
- TheProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Functional characterization ofPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- Cell-type-specific regulation of APOE and CLU levels in human neurons by the Alzheimer's disease risk gene SORL1.Cell reports · 2023Article
- Anticholinergic drugs and dementia risk: Using stem cell-based studies to complement pharmacoepidemiology.Alzheimer's & dementia (New York, N. Y.)Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The SORL1 gene (SORLA) is strongly associated with risk of developing Alzheimer's disease (AD). SORLA is a regulator of endosomal trafficking in neurons and interacts with retromer, a complex that is a "master conductor" of endosomal trafficking. Small molecules can increase retromer expression in vitro, enhancing its function. We treated hiPSC-derived cortical neurons that are either fully deficient, haploinsufficient, or that harbor one copy of SORL1 variants linked to AD with TPT-260, a retromer-enhancing molecule. We show significant increases in retromer subunit VPS26B expression. We tested whether endosomal, amyloid, and TAU pathologies were corrected. We observed that the degree of rescue by TPT-260 treatment depended on the number of copies of functional SORL1 and which SORL1 variant was expressed. Using a disease-relevant preclinical model, our work illuminates how the SORL1-retromer pathway can be therapeutically harnessed.
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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.