ArticleMolecular medicine reports2017
Activation of Sonic hedgehog signal by Purmorphamine, in a mouse model of Parkinson's disease, protects dopaminergic neurons and attenuates inflammatory response by mediating PI3K/AKt signaling pathway.
Article in Molecular medicine reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- The Therapeutic Potential of Purmorphamine Across Disease Models.Journal of cellular and molecular medicine · 2026Review
- Review
- Sonic Hedgehog-Gli1 signaling promotes microglial activation via the IKKβ/NF-κB pathway.Acta pharmacologica Sinica · 2026Article
- Research progress on the Sonic Hedgehog signaling pathway in the central nervous system: Novel insights.Neural regeneration research · 2026Article
- Glycogen Synthase Kinase-3β Mediates Suppression of Neurite Outgrowth Through Sonic Hedgehog Signalling in Palmitic Acid-Exposed Neuro2A Cells.Molecular neurobiology · 2026Article
- Brain transcriptomics highlight abundant gene expression and splicing alterations in non-neuronal cells in aFTLD-U.Acta neuropathologica · 2025Article
- Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations.Molecular neurobiology · 2025Review
- WIF-1 contributes to lupus-induced neuropsychological deficits via the CRYAB/STAT4-SHH axis.Arthritis research & therapy · 2024Article
- Exploring potential developmental origins of common neurodegenerative disorders.Biochemical Society transactions · 2024Review
- Primary cilia in Parkinson's disease: summative roles in signaling pathways, genes, defective mitochondrial function, and substantia nigra dopaminergic neurons.Frontiers in aging neuroscience · 2024Review
- Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms.Molecules (Basel, Switzerland) · 2023Review
- Article
- Therapeutic potential of melatonin and its derivatives in aging and neurodegenerative diseases.Biogerontology · 2023Review
- Sirt1 regulates microglial activation and inflammation following oxygen-glucose deprivation/reoxygenation injury by targeting the Shh/Gli-1 signaling pathway.Molecular biology reports · 2023Article
- From 2D to 3D: Development of Monolayer Dopaminergic Neuronal and Midbrain Organoid Cultures for Parkinson's Disease Modeling and Regenerative Therapy.International journal of molecular sciences · 2023Review
- Primary cilia and SHH signaling impairments in human and mouse models of Parkinson's disease.Nature communications · 2022Article
- Understanding Abnormal SMO-SHH Signaling in Autism Spectrum Disorder: Potential Drug Target and Therapeutic Goals.Cellular and molecular neurobiology · 2022Review
- Human immunodeficiency virus-1 Tat exerts its neurotoxic effects by downregulating Sonic hedgehog signaling.Journal of neurovirology · 2022Article
- Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder.Brain sciences · 2022Article
- Molecular mechanisms of developmental pathways in neurological disorders: a pharmacological and therapeutic review.Open biology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Parkinson's disease (PD), microglial activation-mediated neuroinflammation is associated with dopaminergic neurons degeneration in the substantia nigra pars compacta. Previous studies that have investigated this neurodegenerative disease have reported that the Sonic hedgehog (SHH) signaling pathway, through inhibiting the inflammatory processes, exerts a beneficial neuroprotective effect. However, the mechanisms underlying the anti‑inflammatory and neuroprotective effects of this signaling pathway remain poorly understood. The present study aimed to further investigate these mechanisms in vitro and in vivo. At first, BV2 microglial cells treated with lipopolysaccharide (LPS) were used to induce an inflammatory response. It was observed that the activation of SHH signaling by Purmorphamine attenuated the LPS‑induced inflammatory response, increased the expression of transforming growth factor‑β1 through the phosphatidylinositol 3‑kinase (PI3K)/AKT serine/threonine kinase (Akt) intracellular signaling pathway and inhibited nuclear receptor subfamily 4 group A member 2, independently of the PI3K/Akt signaling pathway. Furthermore, the blockade of the PI3K/Akt signaling pathway by intranasal administration of LY294002, significantly reduced the SHH‑associated neuroprotective effects on dopaminergic neurons, improved motor functions, and increased the microglial activation and inflammatory response in a mouse model of PD induced using 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine. In conclusion, the data of the present study reported that anti‑inflammatory and neuroprotective effects can be obtained in BV2 microglial cells and in a mouse model of PD by successive activation of the SHH and PI3K/Akt signaling pathways.
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