ArticleNature communications2022
Primary cilia and SHH signaling impairments in human and mouse models of Parkinson's disease.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 63 citations in OpenAlex.
- Review
- Article
- Single-cell analysis reveals impaired Müller glia-mediated intercellular communication and photoreceptor pathology in USH1C retinal organoids.Cellular and molecular life sciences : CMLS · 2026Article
- Filippi syndrome-associated CKAP2L modulates microtubule dynamics essential for mitosis and ciliary length regulation.Journal of molecular cell biology · 2026Article
- 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
- Proximity proteomics reveals a co-evolved LRRK2-regulatory network linked to centrosomes.EMBO reports · 2026Article
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- The GPCR Smoothened on cholinergic interneurons modulates dopamine-associated acetylcholine dynamics, learning, and effort management.iScience · 2026Article
- Pathophysiological significance of cholesterol in ciliopathies.Fujita medical journal · 2026Article
- HPV-Driven Cervical Carcinogenesis: Genetic and Epigenetic Mechanisms and Diagnostic Approaches.International journal of molecular sciences · 2026Review
- Emerging roles of the ciliary-mitochondrial axis in cellular homeostasis and neuroprotection.Molecular neurodegeneration advances · 2025Article
- Article
- Cilia at the crossroad: convergence of regulatory mechanisms to govern cilia dynamics during cell signaling and the cell cycle.Cell & bioscience · 2025Review
- Mutations in NEK1 cause ciliary dysfunction as a novel pathogenic mechanism in amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Article
- Tet2 loss and enhanced ciliogenesis suppress α-synuclein pathology.Acta neuropathologica communications · 2025Article
- Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Differences in neuronal ciliation rate and ciliary content revealed by systematic imaging-based analysis of hiPSC-derived models across protocols.Frontiers in cell and developmental biology · 2025Article
- Identification of Key Genes in Esketamine's Therapeutic Effects on Perioperative Neurocognitive Disorders via Transcriptome Sequencing.Drug design, development and therapy · 2025Article
- Sonic Hedgehog Mediates High Frequency-Dependent Deep Brain Stimulation for the Correction of Motor Deficits in a Parkinson's Disease Model.Neuroscience bulletin · 2024Article
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Authors and funding
24 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) as a progressive neurodegenerative disorder arises from multiple genetic and environmental factors. However, underlying pathological mechanisms remain poorly understood. Using multiplexed single-cell transcriptomics, we analyze human neural precursor cells (hNPCs) from sporadic PD (sPD) patients. Alterations in gene expression appear in pathways related to primary cilia (PC). Accordingly, in these hiPSC-derived hNPCs and neurons, we observe a shortening of PC. Additionally, we detect a shortening of PC in PINK1-deficient human cellular and mouse models of familial PD. Furthermore, in sPD models, the shortening of PC is accompanied by increased Sonic Hedgehog (SHH) signal transduction. Inhibition of this pathway rescues the alterations in PC morphology and mitochondrial dysfunction. Thus, increased SHH activity due to ciliary dysfunction may be required for the development of pathoetiological phenotypes observed in sPD like mitochondrial dysfunction. Inhibiting overactive SHH signaling may be a potential neuroprotective therapy for sPD.
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