Dyskinesia in Parkinson’s Disease Therapy
1Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy
2Department of Pharmacology, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
3Department of Neuroscience, Karolinska Institute, Retzius väg 8, 17177 Stockholm, Sweden
Dyskinesia in Parkinson’s Disease Therapy
Description
L-DOPA remains the antiparkinsonian drug of choice due to its superior therapeutic efficacy when compared with alternative treatments, such as dopamine agonists. However, long-term treatment with L-DOPA and, to a lesser extent, with dopamine agonists is challenged by a host of motor side effects. Among them dyskinesia, described as dystonic and choreic involuntary movements, is the most prominent and invalidating.
Several mechanisms underlying dyskinesia have been identified in the last decade. As disease progresses, the massive dopaminergic degeneration results in the loss of buffering capacity by the remaining dopamine neurons, which produces a discontinuous stimulation of dopamine receptors. Moreover, the medium spiny neurons of the striatum react to the loss of dopamine by developing a strong hyperresponsiveness to dopaminergic medications. These factors lead to a plethora of neurophysiological changes within the basal ganglia circuit, accompanied by maladaptive plasticity and profound alterations of the postsynaptic signaling cascades. Importantly, in addition to dopamine, other neurotransmitters and neuromodulators contribute to the development of dyskinesia.
Current interventions to treat dyskinesia are mainly based on continuous delivery of L-DOPA, administration of glutamatergic drugs (i.e., amantadine), replacement or combined administration of L-DOPA with less dyskinetic, albeit less effective, dopaminergic agonists, and deep-brain stimulation of discrete regions of the basal ganglia. Preclinical research on the other hand is searching for novel approaches to dyskinesia treatment, targeting alternative neurotransmitter systems, as the serotonin, adenosine, cannabinoid, or opioid transmission, or identifying critical molecular targets in the postsynaptic cascade.
This special issue mainly focuses on preclinical findings concerning neurophysiological and molecular aspects of dyskinesia, which may offer novel approaches to the management of such disabling side effect of Parkinson's disease therapy. Clinical aspects are also discussed, with particular emphasis on graft-related dyskinesia. Potential topics include, but are not limited to:
- Basal ganglia neurophysiology
- Molecular basis of dyskinesia: pre- and postsynaptic aspects
- Nondopaminergic systems involved in the generation of dyskinesia
- Novel intervention strategies
- Behavioural aspects of dyskinesia and experimental models
- Clinical aspects and management of dyskinesias
- Dyskinesia in human trials of cell transplantation
Before submission authors should carefully read over the journal's Author Guidelines, which are located at http://www.hindawi.com/journals/pd/guidelines/. Prospective authors should submit an electronic copy of their complete manuscript through the journal Manuscript Tracking System at http://mts.hindawi.com/ according to the following timetable: