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

@article{Nizzardo2011BetalactamAO,  title={Beta-lactam antibiotic offers neuroprotection in a spinal muscular atrophy model by multiple mechanisms},  author={Monica Nizzardo and Martina Nardini and Dario Ronchi and Sabrina Salani and Chiara Donadoni and Francesco Fortunato and Giorgia Colciago and Marianna Falcone and Chiara Simone and Giulietta Maria Riboldi and Alessandra Govoni and N Bresolin and Giacomo P Comi and Stefania Corti},  journal={Experimental Neurology},  year={2011},  volume={229},  pages={214-225},  url={https://api.semanticscholar.org/CorpusID:47567316}}

39 Citations

IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

Perinatal administration of IPLEX results in reduced degeneration of MNs, increased muscle fiber size and in amelioration of motor functions in SMA mice, indicating IPLEx as a good therapeutic candidate to hinder the progression of the neurodegenerative process in S MA.

Therapeutic strategies for the treatment of spinal muscular atrophy.

Targeted therapeutic approaches primarily focus on increasing the levels of full-length SMN protein, through either gene replacement or regulation of SMN2 expression, through the preclinical and clinical testing stages.

Drug Screening and Drug Repositioning as Promising Therapeutic Approaches for Spinal Muscular Atrophy Treatment

Interestingly, among the identified molecules by DS/DR in the context of SMA, besides the modulators of SMN2 transcription, it is highlighted a convergence of some targeted molecular cascades contributing to SMA pathology, including cell death related-pathways, mitochondria and cytoskeleton dynamics, neurotransmitter and hormone modulation.

Neuroprotective Effect of Ceftriaxone on MPTP-Induced Parkinson's Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota

It is shown that ceftriaxone exerts a neuroprotective effect in an MPTP-induced PD mouse model, and its neuroProtective effect could be through regulating inflammation and intestinal microbiota.

Spinal Muscular Atrophy: From Gene Discovery to Clinical Trials

A comprehensive and up-to‐date review integrating advances in molecular pathophysiology and diagnostic testing with therapeutic developments for this disease including promising candidates from recent clinical trials is provided.

57 References

β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression

Using a blinded screen of 1,040 FDA-approved drugs and nutritionals, it is discovered that many β-lactam antibiotics are potent stimulators of GLT1 expression, and this action appears to be mediated through increased transcription of theGLT1 gene.

Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy.

Results indicate that the hydroxamic acid class of HDAC inhibitors activates SMN2 gene expression in vivo and has an ameliorating effect on the SMA disease phenotype when administered after disease onset.

therapeutic strategies

    Biology, Medicine
  • 2010

Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy

Assessing whether SMN2 gene expression can be increased by 4-phenylbutyrate suggested that the compound, owing also to its favorable pharmacological properties, could be a good candidate for the treatment of SMA.

Lentivector-mediated SMN replacement in a mouse model of spinal muscular atrophy.

It is reported that lentivector expressing human SMN was successfully used to restore SMN protein levels in SMA type 1 fibroblasts and extend survival by SMN expression constructs.

Regular Exercise Prolongs Survival in a Type 2 Spinal Muscular Atrophy Model Mouse

Analysis at the level of two muscles from the calf, the slow-twitch soleus and the fast-twitch plantaris, showed an overall conserved muscle phenotype in running-trained animals, providing the first evidence for the beneficial effect of exercise in SMA.

Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy.

In fibroblast cultures derived from SMA patients treated with therapeutic doses of valproic acid (VPA), the level of full-length SMN2 mRNA/protein increased 2- to 4-fold, and VPA was able to increase SMN protein levels through transcription activation in organotypic hippocampal brain slices from rats and increased the expression of further SR proteins, which may have important implications for other disorders affected by alternative splicing.

A phase 1 trial of riluzole in spinal muscular atrophy.

This was a limited study with insufficient power to show a difference between the 2 groups, but a suggestion of possible benefit in treated subjects is recommended, and further study of riluzole in pediatric patients with SMA is recommended.
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