Cited by 64Neurogenetic and Muscular Disorders ResearchAmyotrophic Lateral Sclerosis ResearchHereditary Neurological Disorders

Beta-lactam antibiotic offers neuroprotection in a spinal muscular atrophy model by multiple mechanisms

Nizzardo, Monica, Nardini, Martina, Ronchi, Dario, Salani, Sabrina, Donadoni, Chiara, Fortunato, Francesco, Colciago, Giorgia, Falcone, Marianna +6 more·2011·Experimental Neurology

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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Crossref · 10.1016/j.expneurol.2011.01.017

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  1. [1]1. mortality. Arch Dis Child 1970; 45: 33-38. - Lefebvre S, Burglen L, Reboullet S,
  2. [3]3. Am J Hum Genet 1997; 61: 9-15. - Schrank B, Gotz R, Gunnersen JM,
  3. [5]5. the specificity of snRNP assembly. Science 2002; 298: 1775-1779. - Le TT, Pham LT, Butchbach ME,

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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
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
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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