ArticleJournal of molecular neuroscience : MN2012
Sonic hedgehog is cytoprotective against oxidative challenge in a cellular model of amyotrophic lateral sclerosis.
Article in Journal of molecular neuroscience : MN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS.International journal of molecular sciences · 2023Pooled it
- The Therapeutic Potential of Purmorphamine Across Disease Models.Journal of cellular and molecular medicine · 2026Review
- Review
- Changes of Sonic Hedgehog mediated FAK/ERK pathway proteins in amyotrophic lateral sclerosis model mice.Psychopharmacology · 2026Article
- Mutations in NEK1 cause ciliary dysfunction as a novel pathogenic mechanism in amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Article
- Emerging roles of primary cilia in the pathogenesis of amyotrophic lateral sclerosis.Frontiers in neuroscience · 2025Review
- Cilia and Extracellular Vesicles in Brain Development and Disease.Biological psychiatry · 2024Review
- Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism.International journal of molecular sciences · 2024Review
- The role of Smo-Shh/Gli signaling activation in the prevention of neurological and ageing disorders.Biogerontology · 2023Review
- Understanding Abnormal SMO-SHH Signaling in Autism Spectrum Disorder: Potential Drug Target and Therapeutic Goals.Cellular and molecular neurobiology · 2022Review
- Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder.Brain sciences · 2022Article
- Primary cilia and ciliary signaling pathways in aging and age-related brain disorders.Neurobiology of disease · 2022Review
- Exploring Sonic Hedgehog Cell Signaling in Neurogenesis: Its Potential Role in Depressive Behavior.Neurochemical research · 2021Review
- The Role of Sonic Hedgehog Pathway in the Development of the Central Nervous System and Aging-Related Neurodegenerative Diseases.Frontiers in molecular biosciences · 2021Review
- Purmorphamine Attenuates Neuro-Inflammation and Synaptic Impairments After Hypoxic-Ischemic Injury in Neonatal Mice via Shh Signaling.Frontiers in pharmacology · 2020Article
- Clobetasol Modulates Adult Neural Stem Cell Growth via Canonical Hedgehog Pathway Activation.International journal of molecular sciences · 2019Article
- Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond.International journal of molecular sciences · 2018Review
- GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis.Translational neurodegeneration · 2018Article
- Crosstalk between Notch and Sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis.Neuroreport · 2017Article
- Resveratrol Pretreatment Decreases Ischemic Injury and Improves Neurological Function Via Sonic Hedgehog Signaling After Stroke in Rats.Molecular neurobiology · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously demonstrated that primary cilia on spinal motor neurons are reduced in G93A SOD1 (mSOD) mice, a mouse model of amyotrophic lateral sclerosis (ALS). Sonic hedgehog (Shh) signaling involves the primary cilium and Shh has been shown to be cytoprotective in models of other neurodegenerative diseases. Thus, the Shh signaling pathway may bear further study in ALS. Accordingly, we established that interference with the Shh pathway (with the Shh antagonist cyclopamine or with miRNA 3245p) sensitized HT22 cells, while augmentation of the Shh pathway (with Shh or the Shh agonist purmorphamine) protected cells against hydrogen peroxide (H₂O₂) challenge. We ectopically expressed mSOD, human wild-type SOD1 (wtSOD), or an empty vector in HT22 cells. Compared to empty vector, wtSOD decreased cell death and mSOD increased cell death in response to H₂O₂ challenge. Treatment with cyclopamine or miRNA 3245p sensitized all three transfections to H₂O₂ challenge. Treatment with recombinant human Shh or purmorphamine decreased cell death after H₂O₂ challenge, an effect more pronounced in mSOD cells. Compared with empty vector, overexpression of wtSOD increased Shh and Gli transcript levels and increased activity in a Gli-responsive reporter assay. Overexpression of mSOD did not change Shh transcript levels, but decreased Gli transcript levels, especially Gli3, and reduced activity in a Gli reporter assay. These results suggest that overexpression of mSOD but not wtSOD reduces signaling in the Shh pathway and renders mSOD cells more susceptible to H₂O₂ challenge, and that treatment with Shh or Shh agonists is cytoprotective to mSOD cells. Shh or Shh agonists merit further consideration as potential therapy in ALS.
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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.