Beta-lactam antibiotic offers neuroprotection in a spinal muscular atrophy model by multiple mechanisms
Abstract
Spinal muscular atrophy (SMA) is a devastating genetic motoneuron disease leading to infant death. No effective therapy is currently available. It has been suggested that β-lactam antibiotics such as ceftriaxone may offer neuroprotection in motoneuron diseases. Here, we investigate the therapeutic effect of ceftriaxone in a murine model of SMA. Treated animals present a modest, but significant ameliorated neuromuscular phenotype and increased survival, which correlate with protection of neuromuscular units. Whole gene expression profiling in treated mice demonstrates modifications in several genes including those involved in RNA metabolism toward wild-type. The neuroprotective effect seems to be mediated by multiple mechanisms that encompass the increase of the glutamate transporter Glt1, the transcription factor Nrf2, as well as SMN protein. This study provides the first evidence of a potential positive effect of this class of molecules in SMA. Further investigation of analogs with increased and more specific therapeutic effects warrants the development of useful therapies for SMA.
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- Authors
- Nizzardo, M., Nardini, M., Ronchi, D., Salani, S., Donadoni, C., Fortunato, F., Colciago, G., Falcone, M., Simone, C., Riboldi, G., Govoni, A., Bresolin, N., Comi, G. P., & Corti, S.
- Affiliations
- University of Milan (IT)
- Corresponding author
- Corti, Stefania
- ORCID
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 229
- Issue
- 2
- Pages
- 214-225
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2001938328
- Cited by
- 64
- References
- 58
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 8 · 2016: 3 · 2015: 5 · 2014: 10 · 2013: 6 · 2012: 6
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- spinal muscular atrophy, ceftriaxone, beta-lactam antibiotics, neuroprotection, motor neuron disease, Nrf2, SMN protein, RNA metabolism, gene expression profiling, survival
- MeSH terms
- Analysis of Variance, Animals, Anti-Bacterial Agents, Ceftriaxone, Cell Count, Disease Models, Animal, Immunohistochemistry, Mice, Transgenic, Motor Neurons, Muscular Atrophy, Spinal, Spinal Cord, Blotting, Western, Gene Expression, Treatment Outcome, Muscle, Skeletal, Neuroprotective Agents, Reverse Transcriptase Polymerase Chain Reaction, Mice, Kaplan-Meier Estimate, SMN Complex Proteins
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