TY - JOUR
T1 - Research advances on L-DOPA-induced dyskinesia
T2 - from animal models to human disease
AU - Chen, Xi
AU - Wang, Yuanyuan
AU - Wu, Haifeng
AU - Cheng, Cheng
AU - Le, Weidong
N1 - Funding Information:
This work is supported in part by funding from the National Natural Science Foundation of China (NSFC 81430021, NSFC 81771521, and NSFC 81901405).
Publisher Copyright:
© 2020, Fondazione Società Italiana di Neurologia.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - L-3,4-dihydroxyphenylalanine (L-DOPA) was introduced about half a century ago and is still the most effective medicine for the treatment of Parkinson’s disease (PD). However, such chronic treatment eventually leads to L-DOPA-induced dyskinesia (LID) on the majority of PD patients. Besides L-DOPA, dopamine agonists are able to induce dyskinesia as well. So far no drug is yet claimed to effectively curb LID, and amantadine has only a modest benefit on LID patients. Thus, understanding the molecular mechanisms behind LID is urgently needed, and developing new antiparkinsonian medications with low dyskinesia potential is necessarily required. In the last decades, several animal models have been generated for these aims. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned monkey models always considered as gold standard of PD studies are also applied well for the research of LID. Additionally, several rodent models were developed for such clinical needs. Of them, 6-hydroxydopamine (OHDA)-lesioned rats or mice exhibiting countable abnormal involuntary movements (AIMs) after L-DOPA treatments have becoming widely applicable tools for LID pathogenesis studies. Under investigating these models for years, multiple potential LID-associated genes and pathways have been innovatively identified, which largely advance the therapeutic and preventative strategies for the disease. In this review, we attempt to update the recent findings represented in LID animal models and trial studies, which may facilitate the mechanistic understanding, drug development, and clinical evaluation of this movement disorder.
AB - L-3,4-dihydroxyphenylalanine (L-DOPA) was introduced about half a century ago and is still the most effective medicine for the treatment of Parkinson’s disease (PD). However, such chronic treatment eventually leads to L-DOPA-induced dyskinesia (LID) on the majority of PD patients. Besides L-DOPA, dopamine agonists are able to induce dyskinesia as well. So far no drug is yet claimed to effectively curb LID, and amantadine has only a modest benefit on LID patients. Thus, understanding the molecular mechanisms behind LID is urgently needed, and developing new antiparkinsonian medications with low dyskinesia potential is necessarily required. In the last decades, several animal models have been generated for these aims. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned monkey models always considered as gold standard of PD studies are also applied well for the research of LID. Additionally, several rodent models were developed for such clinical needs. Of them, 6-hydroxydopamine (OHDA)-lesioned rats or mice exhibiting countable abnormal involuntary movements (AIMs) after L-DOPA treatments have becoming widely applicable tools for LID pathogenesis studies. Under investigating these models for years, multiple potential LID-associated genes and pathways have been innovatively identified, which largely advance the therapeutic and preventative strategies for the disease. In this review, we attempt to update the recent findings represented in LID animal models and trial studies, which may facilitate the mechanistic understanding, drug development, and clinical evaluation of this movement disorder.
KW - Animal models
KW - Clinical studies
KW - L-DOPA-induced dyskinesia
KW - Parkinson’s disease
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U2 - 10.1007/s10072-020-04333-5
DO - 10.1007/s10072-020-04333-5
M3 - Review article
C2 - 32185625
AN - SCOPUS:85081928068
VL - 41
SP - 2055
EP - 2065
JO - Neurological Sciences
JF - Neurological Sciences
SN - 1590-1874
IS - 8
ER -