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Hum Mol Genet:帕金森氏病新的治疗方法

来源:生物谷 2014-05-19 10:27

近日,约克大学生物学家和心理学家发现治疗帕金森病(PD)的一种潜在新疗法。博士Chris Elliott和Alex Wade博士已经发明了一种技术,可以提供疾病的早期预警。相关研究发表在Human Molecular Genetics杂志上,他们创造了更加敏感的测试,能在退行性变化大规模开始前检测到神经系统变化。

在使用果蝇的实验室测试中,研究人员发现导致帕金森氏的人类基因突变放大年轻果蝇的视觉信号,这导致视力在以后生活中损失。研究人员利用果蝇测试了一种新的药物,靶向帕金森氏突变。这种药物防止果蝇视觉功能的异常改变。

这是第一次该化合物被用于在体内,使用新的灵敏技术对其有效性进行了分析。新的灵敏技术原本是用于测量眼疾病人的视力。Elliott博士说:如果这种药物在临床试验中被证明是成功的,那将带来久缓解帕金森病症状功效,并且比现有左旋多巴疗法有较少的副作用。(生物谷Bioon.com)

Abnormal visual gain control in a Parkinson's Disease model

Farinaz Afsari, et al.

Our understanding of Parkinson's disease (PD) has been revolutionised by the discovery of disease-causing genetic mutations. The most common of these is the G2019S mutation in LRRK2 kinase gene, which leads to increased kinase activity. However, the link between increased kinase activity and PD is unclear.

Previously, we showed that dopaminergic expression of the human LRRK2-G2019S transgene in flies led to an activity-dependent loss of vision in older animals and we hypothesized that this may have been preceded by a failure to regulate neuronal activity correctly in younger animals.

To test this hypothesis, we used a sensitive measure of visual function based on frequency-tagged steady-state visually-evoked potentials (SSVEPs). Spectral analysis allowed us to identify signals from multiple levels of the fly visual system and wild-type visual response curves were qualitatively similar to those from human cortex.

Dopaminergic expression of hLRRK2-G2019S increased contrast sensitivity throughout the retinal network. To test whether this was due to increased kinase activity, we fed Drosophila with kinase inhibitors targeted at LRRK2. Contrast sensitivity in both day1 and day14 flies was normalized by a novel LRRK2 kinase inhibitor ‘BMPPB-32’. Biochemical and cellular assays suggested that BMPPB-32 would be a more specific kinase inhibitor than LRRK2-IN-1. We confirmed this in vivo, finding that dLRRK? null flies show large off-target effects with LRRK2-IN-1 but not BMPPB-32.

Our data link the increased kinase of the G2019S-LRRK2 mutation to neuronal dysfunction and demonstrate the power of the Drosophila visual system in assaying the neurological effects of genetic diseases and therapies.

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