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 summarises the key molecular mechanisms that underlie dyskinesia. The role of dopamine receptors and their associated signaling mechanisms including DARPP-32, ERK, mTOR, MSK-1 and Histone H3 are summarised, along with an evaluation of the role of cannabinoid and nicotinic acetylcholine receptors. The role of synaptic plasticity, and animal behavioural 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 article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.

PMID:

 24773031
[PubMed – as supplied by publisher]