These authors contributed equally to this work.
Dyskinesia in Parkinson's disease: mechanisms and current non-pharmacological interventions
Article first published online: 7 JUN 2014
© 2014 International Society for Neurochemistry
Journal of Neurochemistry
Volume 130, Issue 4, pages 472–489, August 2014
How to Cite
J. Neurochem. (2014) 130, 472–489.
- Issue published online: 7 AUG 2014
- Article first published online: 7 JUN 2014
- Accepted manuscript online: 29 APR 2014 04:41AM EST
- Manuscript Accepted: 27 APR 2014
- Manuscript Revised: 23 APR 2014
- Manuscript Received: 11 DEC 2013
- Spanish Ministries de Economía y Competitividad and of Sanidad Política Social e Igualdad. Grant Number: BFU2010-20664
- CIBERNED. Grant Numbers: CB06/05/0055, CB05/05/505, SAF2007-062262
- Comunidad de Madrid. Grant Number: S2011/BMD-2336
- ICyTDF México
- FIS. Grant Number: PI10-02827
- German Bundesministerium für Bildung und Forschung. Grant Number: 01GN1006B
- Sardinia Regional Government
- cell replacement therapy;
- deep brain stimulation;
- transcranial magnetic field stimulation
Dopamine replacement therapy in Parkinson's disease is associated with several unwanted effects, of which dyskinesia is the most disabling. The development of new therapeutic interventions to reduce the impact of dyskinesia in Parkinson's disease is therefore a priority need. This review summarizes the key molecular mechanisms that underlie dyskinesia. The role of dopamine receptors and their associated signaling mechanisms including dopamine-cAMP-regulated neuronal phosphoprotein, extracellular signal-regulated kinase, mammalian target of rapamycin, mitogen and stress-activated kinase-1 and Histone H3 are summarized, along with an evaluation of the role of cannabinoid and nicotinic acetylcholine receptors. The role of synaptic plasticity and animal behavioral results on dyskinesia are also evaluated. The most recent therapeutic advances to treat Parkinson's disease are discussed, with emphasis on the possibilities and limitations of non-pharmacological interventions such as physical activity, deep brain stimulation, transcranial magnetic field stimulation and cell replacement therapy. The review suggests new prospects for the management of Parkinson's disease-associated motor symptoms, especially the development of dyskinesia.
This review aims at summarizing the key molecular mechanisms underlying dyskinesia and the most recent therapeutic advances to treat Parkinson's disease with emphasis on non-pharmacological interventions such as physical activity, deep brain stimulation (DBS), transcranial magnetic field stimulation (TMS) and cell replacement therapy. These new interventions are discussed from both the experimental and clinical point of view, describing their current strength and limitations.