Roles of the M4 acetylcholine receptor in the basal ganglia and the treatment of movement disorders.
Mov Disord
; 34(8): 1089-1099, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31211471
ABSTRACT
Acetylcholine (ACh) released from cholinergic interneurons acting through nicotinic and muscarinic acetylcholine receptors (mAChRs) in the striatum have been thought to be central for the potent cholinergic regulation of basal ganglia activity and motor behaviors. ACh activation of mAChRs has multiple actions to oppose dopamine (DA) release, signaling, and related motor behaviors and has led to the idea that a delicate balance of DA and mAChR signaling in the striatum is critical for maintaining normal motor function. Consistent with this, mAChR antagonists have efficacy in reducing motor symptoms in diseases where DA release or signaling is diminished, such as in Parkinson's disease and dystonia, but are limited in their utility because of severe adverse effects. Recent breakthroughs in understanding both the anatomical sites of action of ACh and the mAChR subtypes involved in regulating basal ganglia function reveal that the M4 subtype plays a central role in regulating DA signaling and release in the basal ganglia. These findings have raised the possibility that sources of ACh outside of the striatum can regulate motor activity and that M4 activity is a potent regulator of motor dysfunction. We discuss how M4 activity regulates DA release and signaling, the potential sources of ACh that can regulate M4 activity, and the implications of targeting M4 activity for the treatment of the motor symptoms in movement disorders. © 2019 International Parkinson and Movement Disorder Society.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Gânglios da Base
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Acetilcolina
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Dopamina
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Neostriado
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Receptor Muscarínico M4
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Transtornos dos Movimentos
Limite:
Humans
Idioma:
En
Revista:
Mov Disord
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA