ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Inhibition of adenylyl cyclase type 5 prevents L-DOPA-induced dyskinesia in an animal model of Parkinson's disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- Regulating astrocytic activity in the dorsal striatum mitigates L-dopa-induced dyskinesia in Parkinson's disease.Scientific reports · 2025Article
- Adenylyl Cyclases as Therapeutic Targets in Neuroregeneration.International journal of molecular sciences · 2025Review
- Sitagliptin attenuates L-dopa-induced dyskinesia by regulating mitochondrial proteins and neuronal activity in a 6-OHDA-induced mouse model of Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Magea13 attenuates myocardial injury in acute myocardial infarction by inhibiting the cAMP-PKA signaling pathway.Apoptosis : an international journal on programmed cell death · 2025Article
- Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5.Cell reports · 2025Article
- Striatal Subregion-selective Dysregulated Dopamine Receptor-mediated Intracellular Signaling in a Model of DOPA-responsive Dystonia.Neuroscience · 2023Article
- Article
- Article
- Discovery of levodopa-induced dyskinesia-associated genes using genomic studies in patients and Drosophila behavioral analyses.Communications biology · 2022Article
- Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia-Literature Review.Journal of clinical medicine · 2021Review
- β‑Lapachone ameliorates L‑DOPA‑induced dyskinesia in a 6‑OHDA‑induced mouse model of Parkinson's disease.Molecular medicine reports · 2021Article
- Review
- Circuit Mechanisms of L-DOPA-Induced Dyskinesia (LID).Frontiers in neuroscience · 2021Review
- Cannabidiol as a Therapeutic Target: Evidence of its Neuroprotective and Neuromodulatory Function in Parkinson's Disease.Frontiers in pharmacology · 2020Review
- Dereplication of Components Coupled with HPLC-qTOF-MS in the Active Fraction ofMolecules (Basel, Switzerland) · 2019Article
- Effects of histone acetyltransferase inhibitors on L-DOPA-induced dyskinesia in a murine model of Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2018Article
- Signal transduction in L-DOPA-induced dyskinesia: from receptor sensitization to abnormal gene expression.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- Simvastatin Inhibits Activation of NADPH Oxidase/p38 MAPK Pathway and Enhances Expression of Antioxidant Protein in Parkinson Disease Models.Frontiers in molecular neuroscience · 2018Article
- Targeted Interneuron Depletion in the Dorsal Striatum Produces Autism-like Behavioral Abnormalities in Male but Not Female Mice.Biological psychiatry · 2017Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is widely used as a therapeutic choice for the treatment of patients with Parkinson's disease. However, the long-term use of L-DOPA leads to the development of debilitating involuntary movements, called L-DOPA-induced dyskinesia (LID). The cAMP/protein kinase A (PKA) signaling in the striatum is known to play a role in LID. However, from among the nine known adenylyl cyclases (ACs) present in the striatum, the AC that mediates LID remains unknown. To address this issue, we prepared an animal model with unilateral 6-hydroxydopamine lesions in the substantia nigra in wild-type and AC5-knock-out (KO) mice, and examined behavioral responses to short-term or long-term treatment with L-DOPA. Compared with the behavioral responses of wild-type mice, LID was profoundly reduced in AC5-KO mice. The behavioral protection of long-term treatment with L-DOPA in AC5-KO mice was preceded by a decrease in the phosphorylation levels of PKA substrates ERK (extracellular signal-regulated kinase) 1/2, MSK1 (mitogen- and stress-activated protein kinase 1), and histone H3, levels of which were all increased in the lesioned striatum of wild-type mice. Consistently, FosB/ΔFosB expression, which was induced by long-term L-DOPA treatment in the lesioned striatum, was also decreased in AC5-KO mice. Moreover, suppression of AC5 in the dorsal striatum with lentivirus-shRNA-AC5 was sufficient to attenuate LID, suggesting that the AC5-regulated signaling cascade in the striatum mediates LID. These results identify the AC5/cAMP system in the dorsal striatum as a therapeutic target for the treatment of LID in patients with Parkinson's disease.
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