Tolmasov Michael, Djaldetti Ruth, Lev Nirit, Gilgun-Sherki Yossi
a Specialty Products Department , Dexcel Pharma Technologies Ltd ., Jerusalem , Israel.
b Department of Neurology , Rabin Medical Center, Beilinson Campus , Petach Tikva , Israel.
Expert Rev Neurother. 2016 May;16(5):505-13. doi: 10.1586/14737175.2016.1164600. Epub 2016 Mar 25.
Parkinson's disease (PD) and related synucleinopathies are characterized by extensive neuronal cell loss, which is potentially triggered by α-synuclein misfolding and aggregation. Therefore it is reasonable to suggest that treatments targeting α-synuclein could reduce its levels and toxicity, rescue neuronal cells and halt the neurodegeneration process. Several approaches to decrease α-synuclein levels were employed thus far, mainly by using β-synuclein, another protein from the same family, or immunotherapies. These treatments demonstrated some positive results in preclinical studies, which may pave the road to the development of new promising disease-modifying therapies (DMTs). This approach should be further examined in preclinical and clinical settings, together with a clear process in order to advance candidates, enable the ability to define when there are target engagements and to detect what is a meaningful pharmacological response, and how it will be translated in clinical efficacy.
帕金森病（PD）及相关突触核蛋白病的特征是广泛的神经元细胞丢失，这可能由α-突触核蛋白错误折叠和聚集引发。因此，有理由认为针对α-突触核蛋白的治疗可以降低其水平和毒性，挽救神经元细胞并阻止神经退行性变过程。迄今为止，采用了几种降低α-突触核蛋白水平的方法，主要是使用来自同一家族的另一种蛋白质β-突触核蛋白，或免疫疗法。这些治疗在临床前研究中显示出一些积极结果，这可能为开发新的有前景的疾病修饰疗法（DMT）铺平道路。这种方法应在临床前和临床环境中进一步研究，同时要有明确的流程，以便推进候选药物，能够确定何时有靶点参与，检测有意义的药理反应是什么，以及它将如何转化为临床疗效。
