ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Gene expression analyses identify Narp contribution in the development of L-DOPA-induced dyskinesia.
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 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- A small molecule reduces both parkinsonism and l-dopa-induced dyskinesia in animal models of Parkinson's disease.Science translational medicine · 2026Article
- Memory-Associated Immediate Early Genes: Roles in Synaptic Function, Memory Processes, and Neurological Diseases.Molecular neurobiology · 2025Review
- L-DOPA Induces Spatially Discrete Changes in Gene Expression in the Forebrain of Mice with a Progressive Loss of Dopaminergic Neurons.Molecular neurobiology · 2025Article
- Loss of Nocturnin increases neuronal viability in oxidative stress conditions.Frontiers in neuroscience · 2025Article
- Transcriptomic imputation of genetic risk variants uncovers novel whole-blood biomarkers of Parkinson's disease.NPJ Parkinson's disease · 2024Article
- The Gene Expression of Proteins Involved in Intercellular Signaling and Neurodegeneration in the Substantia Nigra in a Mouse Subchronic Model of Parkinson's Disease.International journal of molecular sciences · 2023Article
- Supplementation of dietary areca nut extract modulates the growth performance, cecal microbiota composition, and immune function in Wenchang chickens.Frontiers in veterinary science · 2023Article
- E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2.EMBO reports · 2022Article
- The mitochondrial protein Sideroflexin 3 (SFXN3) influences neurodegeneration pathways in vivo.The FEBS journal · 2022Article
- Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
- Machine Learning-Based Prediction of Impulse Control Disorders in Parkinson's Disease From Clinical and Genetic Data.IEEE open journal of engineering in medicine and biology · 2022Article
- In vitro genome editing rescues parkinsonism phenotypes in induced pluripotent stem cells-derived dopaminergic neurons carrying LRRK2 p.G2019S mutation.Stem cell research & therapy · 2021Article
- All-or-none disconnection of pyramidal inputs onto parvalbumin-positive interneurons gates ocular dominance plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Transcriptomic approach predicts a major role for transforming growth factor beta type 1 pathway in L-Dopa-induced dyskinesia in parkinsonian rats.Genes, brain, and behavior · 2020Article
- Research advances on L-DOPA-induced dyskinesia: from animal models to human disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Review
- Epigenetics in Lewy Body Diseases: Impact on Gene Expression, Utility as a Biomarker, and Possibilities for Therapy.International journal of molecular sciences · 2020Review
- The Basic Characteristics of the Pentraxin Family and Their Functions in Tumor Progression.Frontiers in immunology · 2020Review
- L-DOPA in Parkinson's Disease: Looking at the "False" Neurotransmitters and Their Meaning.International journal of molecular sciences · 2019Review
- Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity: Insights from a Rat Model.Molecular neurobiology · 2019Article
- MTOR Pathway-Based Discovery of Genetic Susceptibility to L-DOPA-Induced Dyskinesia in Parkinson's Disease Patients.Molecular neurobiology · 2019Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Parkinson's disease, long-term dopamine replacement therapy is complicated by the appearance of L-DOPA-induced dyskinesia (LID). One major hypothesis is that LID results from an aberrant transcriptional program in striatal neurons induced by L-DOPA and triggered by the activation of ERK. To identify these genes, we performed transcriptome analyses in the striatum in 6-hydroxydopamine-lesioned mice. A time course analysis (0-6 h after treatment with L-DOPA) identified an acute signature of 709 genes, among which genes involved in protein phosphatase activity were overrepresented, suggesting a negative feedback on ERK activation by l-DOPA. l-DOPA-dependent deregulation of 28 genes was blocked by pretreatment with SL327, an inhibitor of ERK activation, and 26 genes were found differentially expressed between highly and weakly dyskinetic animals after treatment with L-DOPA. The intersection list identified five genes: FosB, Th, Nptx2, Nedd4l, and Ccrn4l. Nptx2 encodes neuronal pentraxin II (or neuronal activity-regulated pentraxin, Narp), which is involved in the clustering of glutamate receptors. We confirmed increased Nptx2 expression after L-DOPA and its blockade by SL327 using quantitative RT-PCR in independent experiments. Using an escalating L-DOPA dose protocol, LID severity was decreased in Narp knock-out mice compared with their wild-type littermates or after overexpression of a dominant-negative form of Narp in the striatum. In conclusion, we have identified a molecular signature induced by L-DOPA in the dopamine-denervated striatum that is dependent on ERK and associated with LID. Here, we demonstrate the implication of one of these genes, Nptx2, in the development of LID.
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