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D1-mGlu5 heteromers...
D1-mGlu5 heteromers mediate noncanonical dopamine signaling in Parkinson’s disease
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- Sebastianutto, Irene (author)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups
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- Goyet, Elise (author)
- University of Montpellier
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- Andreoli, Laura (author)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups
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- Font-Ingles, Joan (author)
- University of Montpellier
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- Moreno-Delgado, David (author)
- UCB Pharma,University of Montpellier
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- Bouquier, Nathalie (author)
- University of Montpellier
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- Jahannault-Talignani, Céline (author)
- University of Montpellier
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- Moutin, Enora (author)
- University of Montpellier
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- Di Menna, Luisa (author)
- Istituto Neurologico Mediterraneo Neuromed
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- Maslava, Natallia (author)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups
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- Pin, Jean Philippe (author)
- University of Montpellier
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- Fagni, Laurent (author)
- University of Montpellier
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- Nicoletti, Ferdinando (author)
- Istituto Neurologico Mediterraneo Neuromed,Sapienza University of Rome
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- Ango, Fabrice (author)
- University of Montpellier
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- Cenci, M. Angela (author)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups
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- Perroy, Julie (author)
- University of Montpellier
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(creator_code:org_t)
- 2020
- 2020
- English.
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In: Journal of Clinical Investigation. - 0021-9738. ; 130:3, s. 1168-1184
- Related links:
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http://dx.doi.org/10...
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Abstract
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- Dopamine receptor D1 modulates glutamatergic transmission in cortico-basal ganglia circuits and represents a major target of L-DOPA therapy in Parkinson’s disease. Here we show that D1 and metabotropic glutamate type 5 (mGlu5) receptors can form previously unknown heteromeric entities with distinctive functional properties. Interacting with Gq proteins, cell-surface D1-mGlu5 heteromers exacerbated PLC signaling and intracellular calcium release in response to either glutamate or dopamine. In rodent models of Parkinson’s disease, D1-mGlu5 nanocomplexes were strongly upregulated in the dopamine-denervated striatum, resulting in a synergistic activation of PLC signaling by D1 and mGlu5 receptor agonists. In turn, D1-mGlu5–dependent PLC signaling was causally linked with excessive activation of extracellular signal–regulated kinases in striatal neurons, leading to dyskinesia in animals treated with L-DOPA or D1 receptor agonists. The discovery of D1-mGlu5 functional heteromers mediating maladaptive molecular and motor responses in the dopamine-denervated striatum may prompt the development of new therapeutic principles for Parkinson’s disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Sebastianutto, I ...
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Goyet, Elise
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Andreoli, Laura
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Font-Ingles, Joa ...
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Moreno-Delgado, ...
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Bouquier, Nathal ...
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show more...
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Jahannault-Talig ...
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Moutin, Enora
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Di Menna, Luisa
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Maslava, Natalli ...
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Pin, Jean Philip ...
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Fagni, Laurent
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Nicoletti, Ferdi ...
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Ango, Fabrice
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Cenci, M. Angela
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Perroy, Julie
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Journal of Clini ...
- By the university
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Lund University