ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Rapamycin delays disease onset and prevents PrP plaque deposition in a mouse model of Gerstmann-Sträussler-Scheinker disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 106 citations in OpenAlex.
- Prion propagation is controlled by a hierarchical network involving the nuclear Tfap2c and hnRNP K factors and the cytosolic mTORC1 complex.PLoS pathogens · 2026Article
- Contrasting roles of autophagy in cellular prion infection.Autophagy · 2025Article
- Retinitis Pigmentosa-Associated Gene TRIM49 Regulates ULK1-Mediated Autophagy and Photoreceptor Phagocytosis by the Retinal Pigment Epithelium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Autophagy in cancer and protein conformational disorders.FEBS letters · 2025Review
- Microglia-specific NF-κB signaling is a critical regulator of prion-induced glial inflammation and neuronal loss.PLoS pathogens · 2025Article
- New Therapeutic Modalities in Prion Diseases.Sub-cellular biochemistry · 2025Review
- Therapeutic Trajectories in Human Prion Diseases.Sub-cellular biochemistry · 2025Review
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Anti-prion drugs do not improve survival in novel knock-in models of inherited prion disease.PLoS pathogens · 2024Article
- Targeting the biology of aging with mTOR inhibitors.Nature aging · 2023Review
- Neurodegeneration, Mitochondria, and Antibiotics.Metabolites · 2023Review
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Brain aging is faithfully modelled in organotypic brain slices and accelerated by prions.Communications biology · 2022Article
- Proteostasis unbalance in prion diseases: Mechanisms of neurodegeneration and therapeutic targets.Frontiers in neuroscience · 2022Review
- SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K/AKT/mTOR signaling.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- MicroRNAs in Prion Diseases-From Molecular Mechanisms to Insights in Translational Medicine.Cells · 2021Review
- AMPK activation does not enhance autophagy in neurons in contrast to MTORC1 inhibition: different impact on β-amyloid clearance.Autophagy · 2021Article
- A New Take on Prion Protein Dynamics in Cellular Trafficking.International journal of molecular sciences · 2020Review
- Activate or Inhibit? Implications of Autophagy Modulation as a Therapeutic Strategy for Alzheimer's Disease.International journal of molecular sciences · 2020Review
- From Seeds to Fibrils and Back: Fragmentation as an Overlooked Step in the Propagation of Prions and Prion-Like Proteins.Biomolecules · 2020Review
1 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
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Abstract
Autophagy is a cell survival response to nutrient deprivation that delivers cellular components to lysosomes for digestion. In recent years, autophagy has also been shown to assist in the degradation of misfolded proteins linked to neurodegenerative disease (Ross and Poirier, 2004). In support of this, rapamycin, an autophagy inducer, improves the phenotype of several animal models of neurodegenerative disease. Our Tg(PrP-A116V) mice model Gerstmann-Sträussler-Scheinker disease (GSS), a genetic prion disease characterized by prominent ataxia and extracellular PrP amyloid plaque deposits in brain (Yang et al., 2009). To determine whether autophagy induction can mitigate the development of GSS, Tg(PrP-A116V) mice were chronically treated with 10 or 20 mg/kg rapamycin intraperitoneally thrice weekly, beginning at 6 weeks of age. We observed a dose-related delay in disease onset, a reduction in symptom severity, and an extension of survival in rapamycin-treated Tg(PrP-A116V) mice. Coincident with this response was an increase in the autophagy-specific marker LC3II, a reduction in insoluble PrP-A116V, and a near-complete absence of PrP amyloid plaques in the brain. An increase in glial cell apoptosis of unclear significance was also detected. These findings suggest autophagy induction enhances elimination of misfolded PrP before its accumulation in plaques. Because ataxia persisted in these mice despite the absence of plaque deposits, our findings also suggest that PrP plaque pathology, a histopathological marker for the diagnosis of GSS, is not essential for the GSS phenotype.
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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.