Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome
Open accessAbstract
Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is widely prescribed for the treatment of high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent one of the robust functional consequences of increased protein synthesis in FXS, epileptogenesis. These data suggest that lovastatin is potentially disease modifying and could be a viable prophylactic treatment for epileptogenesis in FXS.
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Treatment with lovastatin dampens neuronal hyperexcitability in the brain of Fmr1 KO mice and rescues part of the mouse FXS phenotype.
“Treatment with lovastatin, an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase which regulates the early irreversible and rate-limiting step in the biosynthesis of cholesterol, dampens neuronal hyperexcitability in the brain of FXS mouse model, Fmr1 KO mice, and rescues part of the mouse FXS phenotype14.”
From An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis (2023) · cites this paper as [14]
Statin treatment might improve behavioral outcomes in FXS children and lovastatin has beneficial effects on the phenotype of Fmr1 KO mice.
“Statin treatment might improve behavioral outcomes in FXS children16,17 and lovastatin has beneficial effects on the phenotype of Fmr1 KO mice14.”
From An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis (2023) · cites this paper as [14]
Microglia recycle neuronal cholesterol during dendrite pruning.
“Furthermore, microglia, which function as brain macrophages, recycle neuronal cholesterol during dendrite pruning39, and replacing mutant with wild type microglia via bone marrow transfer ameliorated RTT symptoms in Mecp2 null mice13.”
From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [39]
The Results passage on hippocampal-slice epileptogenesis and the Discussion passage on fragile X symptoms address lovastatin, protein synthesis, and seizures, not microglia or cholesterol recycling. Searches for microglia, neuronal cholesterol, and dendrite pruning found no passage in our copy addressing the attributed claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredStudies of lovastatin treatment in the FXS knock out (KO) mouse rescued excess protein synthesis and also epilepsy.
“Studies of lovastatin treatment in the FXS knock out (KO) mouse rescued excess protein synthesis and also epilepsy [113].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [113]
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- Authors
- Osterweil, E. K., Chuang, S.-C., Chubykin, A. A., Sidorov, M., Bianchi, R., Wong, R. K. S., & Bear, M. F.
- Affiliations
- Howard Hughes Medical Institute (US)
- SUNY Downstate Health Sciences University (US)
- Corresponding author
- Bear, Mark F.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 77
- Issue
- 2
- Pages
- 243-250
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3597444
- OpenAlex
- W2156319664
- Cited by
- 230
- References
- 37
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 18 · 2023: 9 · 2022: 13 · 2021: 15 · 2020: 25 · 2019: 17 · 2018: 12 · 2017: 28 · 2016: 17 · 2015: 21 · 2014: 22 · 2013: 18
- FWCI
- 17.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 387 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- Simons Foundation
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute of Mental Health
- FRAXA Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- lovastatin, fragile X syndrome, epileptogenesis, protein synthesis, hippocampus, synaptic regulation, disease-modifying therapy, prophylaxis, statins, neuropsychiatric symptoms
- MeSH terms
- Animals, Disease Models, Animal, Epilepsy, Fragile X Syndrome, Lovastatin, Male, Mice, Inbred C57BL, Protein Biosynthesis, Mice, Knockout, Mice
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