Aberrant Rac1-cofilin signaling mediates defects in dendritic spines, synaptic function, and sensory perception in fragile X syndrome
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Inhibiting Rac1-PAK-LIMK signaling may restore synaptic function and sensory processing in patients with fragile X syndrome.
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Rac1 is a converging factor downstream of numerous proteins encoded by high-risk ASD genes.
“Rac1 has been identified as a converging factor downstream of numerous proteins encoded by high-risk ASD genes, such as SHANK 4–6, FMR1 (fragile X mental retardation-1) 7, 8, NRXN 9, and AUTS2 10.”
From Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. (2021) · cites this paper as [7]
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- Authors
- Pyronneau, A., He, Q., Hwang, J.-Y., Porch, M., Contractor, A., & Zukin, R. S.
- Affiliations
- Albert Einstein College of Medicine (US)
- Northwestern University (US)
- Corresponding author
- Zukin, R. Suzanne
- Venue
- Science Signaling
- Published
- 2017-11-07
- Volume
- 10
- Issue
- 504
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC5988355
- OpenAlex
- W2767737184
- Cited by
- 122
- References
- 78
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 14 · 2023: 17 · 2022: 10 · 2021: 24 · 2020: 17 · 2019: 14 · 2018: 11 · 2017: 1
- FWCI
- 7.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (award304400, MH092877, award304548, NS45693, award304549, HD083828, award304565, GM007288)
- National Institute of Mental Health (award304564, MH108362, award308817, R21MH104808)
- Brain and Behavior Research Foundation (award304558, Distinguished Investigator Grant, award304563, Young Investigator Grant)
- McKnight Foundation (award304550)
- National Institute of General Medical Sciences (award316793, T32-GM007822)
- American Heart Association (award304562, Scientist Development Grant)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- fragile X syndrome, Rac1, cofilin, PAK1, dendritic spines, synaptic function, sensory perception, layer 5 pyramidal neurons, small molecule inhibitors, spine density, FMRP
- MeSH terms
- Actins, Animals, Disease Models, Animal, Fragile X Syndrome, Neuropeptides, Perception, Phosphorylation, Pyridones, Pyrimidines, Somatosensory Cortex, Synapses, Pyramidal Cells, Mice, Knockout, rac1 GTP-Binding Protein, Dendritic Spines, Cofilin 1, Mice, p21-Activated Kinases
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