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Abstract：
One of the biggest problems in the treatment of idiopathic Parkinson\'s disease is the lack of new drugs that slow its progression. L-Dopa remains the star drug in the treatment of this disease, although it induces severe side effects. The failure of clinical studies with new drugs depends on the use of preclinical models based on neurotoxins that do not represent what happens in the disease since they induce rapid and expansive neurodegeneration. We have recently proposed a single-neuron degeneration model for idiopathic Parkinson\'s disease that requires years to accumulate enough lost neurons for the onset of motor symptoms. This single-neuron degeneration model is based on the excessive formation of aminochrome during neuromelanin synthesis that surpass the neuroprotective action of the enzymes DT-diaphorase and glutathione transferase M2-2, which prevent the neurotoxic effects of aminochrome. Although the neurotoxic effects of aminochrome do not have an expansive effect, a stereotaxic injection of this endogenous neurotoxin cannot be used to generate a preclinical model in an animal. Therefore, the aim of this review is to evaluate the strategies for pharmacologically increasing the expression of DT diaphorase and GSTM2-2 and molecules that induce the expression of vesicular monoamine transporter 2, such as pramipexole.
摘要：
治疗特发性帕金森病的最大问题之一是缺乏减缓其进展的新药。左旋多巴仍然是治疗这种疾病的明星药物，虽然会引起严重的副作用.新药临床研究的失败取决于基于神经毒素的临床前模型的使用，这些神经毒素不代表疾病中发生的事情，因为它们引起快速和扩张性的神经变性。我们最近提出了一种特发性帕金森病的单神经元变性模型，该模型需要数年才能积累足够的神经元，以使运动症状发作。这种单神经元变性模型是基于神经黑色素合成过程中氨基色素的过度形成，超过了DT-心肌黄递酶和谷胱甘肽转移酶M2-2的神经保护作用，从而阻止了氨基色素的神经毒性作用。虽然氨基色素的神经毒性作用没有膨胀作用，这种内源性神经毒素的立体定向注射不能用于在动物中产生临床前模型。因此,这篇综述的目的是评估药理学上增加DT心肌黄递酶和GSTM2-2表达的策略,以及诱导囊泡单胺转运蛋白2表达的分子,如普拉克索.
