ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
IGF-1R Reduction Triggers Neuroprotective Signaling Pathways in Spinal Muscular Atrophy Mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Antisense oligonucleotides treatment uncovers differences in the modulation of dysregulated intracellular pathways in Spinal Muscular Atrophy motoneurons.Cell death & disease · 2026Article
- Drug Candidate BIO101 for Spinal Muscular Atrophy as Monotherapy or Combined With the Antisense Oligonucleotide ASO-10-27.Journal of cachexia, sarcopenia and muscle · 2025Article
- The Effect of Aerobic Exercise Training on Patients with Type III Spinal Muscular Atrophy.Journal of clinical medicine · 2025Article
- The Role of mTOR in Amyotrophic Lateral Sclerosis.Biomedicines · 2025Review
- Amyotrophic Lateral Sclerosis (ALS): An Overview of Genetic and Metabolic Signaling Mechanisms.CNS & neurological disorders drug targets · 2025Review
- Revealing the potential role of hsa-miR-663a in modulating the PI3K-Akt signaling pathway via miRNA microarray in spinal muscular atrophy patient fibroblast-derived iPSCs.Journal of neuropathology and experimental neurology · 2024Article
- A role for astrocytic insulin-like growth factor I receptors in the response to ischemic insult.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Administration of adipose-derived stem cells extracellular vesicles in a murine model of spinal muscular atrophy: effects of a new potential therapeutic strategy.Stem cell research & therapy · 2024Article
- The Role of Insulin-like Growth Factor I in Mechanisms of Resilience and Vulnerability to Sporadic Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- ERK MAPK signaling pathway inhibition as a potential target to prevent autophagy alterations in Spinal Muscular Atrophy motoneurons.Cell death discovery · 2023Article
- NADPH oxidase 4 inhibition is a complementary therapeutic strategy for spinal muscular atrophy.Frontiers in cellular neuroscience · 2023Article
- IGF/IGF-1R signal pathway in pain: a promising therapeutic target.International journal of biological sciences · 2023Review
- Recent research on the treatment of spinal muscular atrophy.Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022Review
- Spinal muscular atrophy: Broad disease spectrum and sex-specific phenotypes.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- AAV9-DOK7 gene therapy reduces disease severity in SmnBiochemical and biophysical research communications · 2020Article
- IGF1R regulates retrograde axonal transport of signalling endosomes in motor neurons.EMBO reports · 2020Article
- The First Orally Deliverable Small Molecule for the Treatment of Spinal Muscular Atrophy.Neuroscience insights · 2020Review
- Muscle regulates mTOR dependent axonal local translation in motor neurons via CTRP3 secretion: implications for a neuromuscular disorder, spinal muscular atrophy.Acta neuropathologica communications · 2019Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by the selective loss of spinal motor neurons due to the depletion of the survival of motor neuron (SMN) protein. No therapy is currently available for SMA, which represents the leading genetic cause of death in childhood. In the present study, we report that insulin-like growth factor-1 receptor (Igf-1r) gene expression is enhanced in the spinal cords of SMA-like mice. The reduction of expression, either at the physiological (through physical exercise) or genetic level, resulted in the following: (1) a significant improvement in lifespan and motor behavior, (2) a significant motor neuron protection, and (3) an increase in SMN expression in spinal cord and skeletal muscles through both transcriptional and posttranscriptional mechanisms. Furthermore, we have found that reducing IGF-1R expression is sufficient to restore intracellular signaling pathway activation profile lying downstream of IGF-1R, resulting in both the powerful activation of the neuroprotective AKT/CREB pathway and the inhibition of the ERK and JAK pathways. Therefore, reducing rather than enhancing the IGF-1 pathway could constitute a useful strategy to limit neurodegeneration in SMA. SIGNIFICANCE STATEMENT: Recent evidence of IGF-1 axis alteration in spinal muscular atrophy (SMA), a very severe neurodegenerative disease affecting specifically the motor neurons, have triggered a renewed interest in insulin-like growth factor-1 (IGF-1) pathway activation as a potential therapeutic approach for motor neuron diseases. The present study challenges this point of view and brings the alternative hypothesis that reducing rather than enhancing the IGF-1 signaling pathway exerts a neuroprotective effect in SMA. Furthermore, the present data substantiate a newly emerging concept that the modulation of IGF-1 receptor expression is a key event selectively determining the activation level of intracellular pathways that lie downstream of the receptor. This aspect should be considered when designing IGF-1-based treatments for neurodegenerative diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.