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

• Published in: Journal of neurochemistry 2014-08, Vol.130 (4), p.472-489
• Main Authors: Heumann, Rolf, Moratalla, Rosario, Herrero, Maria Trinidad, Chakrabarty, Koushik, Drucker‐Colín, René, Garcia‐Montes, Jose Ruben, Simola, Nicola, Morelli, Micaela
• Format: Article
• Language: English
• Subjects: Animals; Cannabinoids - pharmacology; cell replacement therapy; Cell Transplantation; Chromatin - drug effects; Deep Brain Stimulation; Dopamine; Dopamine Agents - therapeutic use; Dopamine and cAMP-Regulated Phosphoprotein 32 - physiology; Dyskinesias - etiology; Dyskinesias - physiopathology; Dyskinesias - therapy; exercise; Histones - metabolism; Humans; Levodopa - pharmacology; Levodopa - therapeutic use; L‐DOPA; Magnetic fields; Motor Activity - physiology; Neurochemistry; Parkinson Disease - complications; Parkinson Disease - physiopathology; Parkinson Disease - therapy; Parkinson's disease; Phosphorylation; Psychomotor Performance - physiology; Receptors, Dopamine D1 - drug effects; Receptors, Dopamine D1 - metabolism; Signal Transduction - drug effects; striatum; transcranial magnetic field stimulation; Transcranial Magnetic Stimulation
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.12751

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. 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.