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Dyskinesia in Parkinson's disease: mechanisms and current non‐pharmacological interventions
Author(s) -
Heumann Rolf,
Moratalla Rosario,
Herrero Maria Trinidad,
Chakrabarty Koushik,
DruckerColín René,
GarciaMontes Jose Ruben,
Simola Nicola,
Morelli Micaela
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12751
Subject(s) - neuroscience , dyskinesia , deep brain stimulation , parkinson's disease , medicine , transcranial magnetic stimulation , paroxysmal dyskinesia , psychology , disease , 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.