ReviewParkinson's disease2016
Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity: A Hypothesis Based on an Unexpected Finding.
Review in Parkinson's disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 24 citations in OpenAlex.
- Protein Aggregates as Drivers of Receptor Clustering and Pathological Signaling: A Framework Linking Extracellular Amyloid-β to Tau Dysregulation.ACS chemical neuroscience · 2026Review
- Effect of Sirt3 on hippocampal MnSOD activity, mitochondrial function, physiology, and cognition in an aged murine model.Behavioural brain research · 2023Article
- Study of Early Onset Schizophrenia: Associations ofLife (Basel, Switzerland) · 2021Article
- 5-Hydroxytryptamine Receptors and Tardive Dyskinesia in Schizophrenia.Frontiers in molecular neuroscience · 2020Article
- l-DOPA and Its Receptor GPR143: Implications for Pathogenesis and Therapy in Parkinson's Disease.Frontiers in pharmacology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A serendipitous pharmacogenetic finding links the vulnerability to developing levodopa-induced dyskinesia to the age of onset of Huntington's disease. Huntington's disease is caused by a polyglutamate expansion of the protein huntingtin. Aberrant huntingtin is less capable of binding to a member of membrane-associated guanylate kinase family (MAGUKs): postsynaptic density- (PSD-) 95. This leaves more PSD-95 available to stabilize NR2B subunit carrying NMDA receptors in the synaptic membrane. This results in increased excitotoxicity for which particularly striatal medium spiny neurons from the indirect extrapyramidal pathway are sensitive. In Parkinson's disease the sensitivity for excitotoxicity is related to increased oxidative stress due to genetically determined abnormal metabolism of dopamine or related products. This probably also increases the sensitivity of medium spiny neurons for exogenous levodopa. Particularly the combination of increased oxidative stress due to aberrant dopamine metabolism, increased vulnerability to NMDA induced excitotoxicity, and the particular sensitivity of indirect pathway medium spiny neurons for this excitotoxicity may explain the observed increased prevalence of levodopa-induced dyskinesia.
Identifiers
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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.