Involvement of canonical and non-canonical D1 dopamine receptor signalling pathways in L-dopa-induced dyskinesia

Chronic L-3,4-dihydroxyphenylalanine (L-dopa) treatment of Parkinson Disease (PD) often leads to debilitating involuntary movements, termed L-dopa-induced dyskinesia (LID). The past few years have seen an unprecedented increase in understanding the neural mechanisms underlying LID manifestation in P...

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Veröffentlicht in:	Parkinsonism & related disorders Jg. 15; S. S64 - S67
Hauptverfasser:	Guigoni, Céline, Bezard, Erwan
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	England Elsevier Ltd 01.12.2009
Schlagworte:	Abnormal involuntary movements Animals Dopamine Agents - adverse effects Dopamine Agents - pharmacology Dopamine D1 receptor Dyskinesia, Drug-Induced - etiology Humans L-dopa Levodopa - adverse effects Levodopa - pharmacology Models, Biological Neurology Parkinson's disease Protein Transport - drug effects Receptors, Dopamine D1 - metabolism Sensitisation Signal Transduction - drug effects Signal Transduction - physiology Trafficking AC D3R Parkinson's disease AMPA L-dopa D1R D2R Trafficking LID RGSL DARPP-32 MSN 6-OHDA SNc cAMP Sensitisation AIMs PD GPCR Dopamine D1 receptor MPTP DA Abnormal involuntary movements ERK extracellular signal-regulated kinase cyclic adenosine 3′,5′-monophosphate D1 dopamine receptor G protein-coupled receptors l-3,4-dihydroxyphenylalanine adenylyl cyclase L-dopa-induced dyskinesia regulatory GPCR signalling protein D2 dopamine receptor dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein, 32 kDa substantia nigra pars compacta D3 dopamine receptor 6-hydroxydopamine α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine medium spiny neurons dopamine
ISSN:	1353-8020, 1873-5126, 1873-5126
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Zusammenfassung:	Chronic L-3,4-dihydroxyphenylalanine (L-dopa) treatment of Parkinson Disease (PD) often leads to debilitating involuntary movements, termed L-dopa-induced dyskinesia (LID). The past few years have seen an unprecedented increase in understanding the neural mechanisms underlying LID manifestation in PD associating them mostly with D1 dopamine (DA) receptor sensitisation and deregulated homologous desensitisation as well as hyperactivity of both canonical and non-canonical DA signalling pathways. We here review these recent findings and demonstrate that decreasing DA receptor-mediated signalling (i) by increasing D1 receptor internalization and (ii) by inhibiting the Ras-Extracellular signal-Regulated Kinase 1/2 non-canonical DA signalling cascade, might reduced LID severity. Strategy (i) uses the lentivirus-mediated over-expression of the G protein-coupled receptor kinase 6 that control the desensitisation of DA receptors. Strategy (ii) proposes to use statins that, besides being specific inhibitors of the rate-limiting enzyme in cholesterol biosynthesis, can also inhibit Ras isoprenylation and activity and subsequently the phosphorylation of ERK1/2. Experiments were performed in both the rodent and primate models of LID. Those results strongly suggest that different strategies might represent a treatment option for managing LID in PD.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	1353-8020 1873-5126 1873-5126
DOI:	10.1016/S1353-8020(09)70783-7