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Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity: A Hypothesis Based on an Unexpected Finding
Joint Authors
Ivanova, Svetlana A.
Loonen, Anton J. M.
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-5, 5 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-04-06
Country of Publication
Egypt
No. of Pages
5
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Ivanova, Svetlana A.& Loonen, Anton J. M.. 2016. Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity: A Hypothesis Based on an Unexpected Finding. Parkinson’s Disease،Vol. 2016, no. 2016, pp.1-5.
https://search.emarefa.net/detail/BIM-1115252
Modern Language Association (MLA)
Ivanova, Svetlana A.& Loonen, Anton J. M.. Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity: A Hypothesis Based on an Unexpected Finding. Parkinson’s Disease No. 2016 (2016), pp.1-5.
https://search.emarefa.net/detail/BIM-1115252
American Medical Association (AMA)
Ivanova, Svetlana A.& Loonen, Anton J. M.. Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity: A Hypothesis Based on an Unexpected Finding. Parkinson’s Disease. 2016. Vol. 2016, no. 2016, pp.1-5.
https://search.emarefa.net/detail/BIM-1115252
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1115252