Dyskinesia in Parkinson's disease: mechanisms and current non-pharmacological interventions

Authors

  • Rolf Heumann,

    1. Molecular Neurobiochemistry, Ruhr-University Bochum, Bochum, Germany
    Search for more papers by this author
    • These authors contributed equally to this work.
  • Rosario Moratalla,

    1. Cajal Institute, CSIC and CIBERNED, ISCIII, Madrid, Spain
    Search for more papers by this author
    • These authors contributed equally to this work.
  • Maria Trinidad Herrero,

    1. Clinical & Experimental Neuroscience (NiCE-CIBERNED), School of Health Sciences, University Jaume I, Castelló, and School of Medicine, University of Murcia, Murcia, Spain
    Search for more papers by this author
  • Koushik Chakrabarty,

    1. Molecular Neurobiochemistry, Ruhr-University Bochum, Bochum, Germany
    Search for more papers by this author
  • René Drucker-Colín,

    1. Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, México
    Search for more papers by this author
  • Jose Ruben Garcia-Montes,

    1. Cajal Institute, CSIC and CIBERNED, ISCIII, Madrid, Spain
    Search for more papers by this author
  • Nicola Simola,

    1. Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy
    Search for more papers by this author
  • Micaela Morelli

    Corresponding author
    1. Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy
    2. National Institute of Neuroscience (INN), University of Cagliari, Cagliari, Italy
    3. National Research Council (CNR), Neuroscience Institute, Cagliari, Italy
    4. Center of Excellence on Neurobiology of Dependence, University of Cagliari, Cagliari, Italy
    • Address correspondence and reprint requests to Micaela Morelli, Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy. E-mail: morelli@unica.it

    Search for more papers by this author

Abstract

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.

image

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.

Ancillary