Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity
| Jazyk: | angličtina |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
n methyl dextro aspartic acid
drug safety glutamate receptor prevalence dopamine metabolism review glutamatergic synapse oxidopamine neurotoxicity synaptic membrane oxidative stress human levodopa long term potentiation extrapyramidal system spinal nerve nonhuman 6 tetrahydro 1 methyl 4 phenylpyridine levodopa-induced dyskinesia n methyl dextro aspartic acid receptor Parkinson disease priority journal tardive dyskinesia dopamine glutamic acid excitotoxicity |
| Zdroj: | Parkinsons disease. 2016:1-5 |
| ISSN: | 2090-8083 |
| DOI: | 10.1155/2016/6461907 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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