Paul Rajib, Borah Anupom
Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam, India.
Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam, India.
Biochim Biophys Acta. 2016 Sep;1860(9):1989-97. doi: 10.1016/j.bbagen.2016.06.018. Epub 2016 Jun 16.
Dopamine replacement therapy by its precursor, L-3.4-dihydroxyphenylalanine (L-DOPA), has been the treatment of choice for Parkinson's disease. However, the possible contributory effect of L-DOPA therapy on the progression of Parkinson's disease mediated by the L-DOPA-induced toxic metabolites remains elusive.
Prolong use of L-DOPA leads to behavioral impediments and instigate the generation of several toxic metabolites. One such metabolite is homocysteine, the level of which increases in the plasma of Parkinson's disease patients undergoing L-DOPA therapy, as well as in brain of animal models of the disease. In concoction with parkinsonian neurotoxins, Hcy exaggerates dopaminergic neurodegeneration, while its intranigral infusion has been demonstrated to decrease the dopamine level as well as causes dopaminergic neurodegeneration. Therefore, it can be propounded that elevated level of Hcy (hyperhomocysteinemia) is one of the underlying causes of L-DOPA-induced side-effects and aggravates the progressive nature of Parkinson's disease, which has been focused here. We have provided a conjectural discussion on the involvement of Hcy in L-DOPA-induced dyskinesia in Parkinson's disease.
Hyperhomocysteinemia as a result of prolonged L-DOPA therapy is the emerging cause of L-DOPA-induced behavioral abnormalities and progressive nature of Parkinson's disease.
This review highlights that hyperhomocysteinemia could be a putative contributor of the side-effects of chronic L-DOPA therapy because of its neurotoxic potency.
通过其前体L-3,4-二羟基苯丙氨酸（L-DOPA）进行多巴胺替代疗法一直是帕金森病的首选治疗方法。然而，L-DOPA疗法通过L-DOPA诱导的毒性代谢产物对帕金森病进展的可能促成作用仍不明确。
长期使用L-DOPA会导致行为障碍，并促使产生多种毒性代谢产物。其中一种代谢产物是同型半胱氨酸，在接受L-DOPA治疗的帕金森病患者血浆以及该疾病动物模型的大脑中，其水平都会升高。与帕金森病神经毒素共同作用时，同型半胱氨酸会加剧多巴胺能神经退行性变，而向黑质内注射同型半胱氨酸已被证明会降低多巴胺水平并导致多巴胺能神经退行性变。因此，可以提出，同型半胱氨酸水平升高（高同型半胱氨酸血症）是L-DOPA诱导的副作用的潜在原因之一，并加剧了帕金森病的进行性发展，本文重点讨论了这一点。我们对同型半胱氨酸在帕金森病L-DOPA诱导的运动障碍中的作用进行了推测性讨论。
长期L-DOPA治疗导致的高同型半胱氨酸血症是L-DOPA诱导的行为异常和帕金森病进行性发展的新出现的原因。
本综述强调，由于其神经毒性作用，高同型半胱氨酸血症可能是慢性L-DOPA治疗副作用的一个推定因素。
