Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases.
Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases.
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DOI：
10.1186/s13065-015-0143-y
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发表时间：
2015
影响因子：
--
通讯作者：
Morgan A
中科院分区：
文献类型：
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作者：
Chen X;Barclay JW;Burgoyne RD;Morgan A
阿尔茨海默氏病等阿尔茨海默氏症相关的神经退行性疾病是一项重大的公共卫生挑战，这是由于社会中老年人比例的人口增长。然而，目前批准用于这些疾病的药物相对较少，仅提供症状缓解。因此，神经退行性疾病研究的一个主要目标是确定潜在的新的治疗化合物，可以通过直接影响神经退行性过程或通过激活随衰老而下降的内源性生理神经保护机制来减缓甚至逆转疾病进展。这需要模型系统，可以概括人类神经退行性疾病的关键特征，也适合化合物筛选方法。哺乳动物模型非常强大，但对于高通量药物筛选来说过于昂贵。鉴于哺乳动物和无脊椎动物之间高度保守的神经通路，秀丽隐杆线虫已成为神经保护化合物筛选的有力工具。在这里，我们描述如何C。Elegans已被用于模拟各种人类衰老相关的神经变性疾病，并提供了在这些蠕虫模型中具有治疗活性并因此可能具有转化潜力的化合物的广泛列表。
Age-associated neurodegenerative disorders such as Alzheimer’s disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential.