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帕金森病的神经保护。

Neuroprotection in Parkinson's disease.

机构信息

University Department of Clinical Neurosciences, Institute of Neurology, UCL, London, UK.

出版信息

Parkinsonism Relat Disord. 2009 Dec;15 Suppl 4:S41-3. doi: 10.1016/S1353-8020(09)70834-X.

Abstract

A major focus in Parkinson's disease (PD) research is to produce drugs or other interventions that can slow or stop clinical progression. This should include an effect on both motor and non-motor symptoms and so target dopaminergic and non-dopaminergic pathways. It is logical to assume that the best chance of developing such therapies will be based on forming a better understanding of the aetiology and pathogenesis of PD and to identify critical molecular targets. There have been great advances in finding different genetic causes and risk factors for PD, but less so in the discovery of environmental contributions. The separate genetic causes still share common pathways to cell dysfunction and death, and these interconnect at several levels. Despite the major advances in genetics and PD pathogenesis, we still do not have good models of PD that can be used with confidence to accurately predict the effect of drugs on disease progression. Clinical trial design and study population selection are also areas that represent significant challenges to testing any putative neuro-protective agent. Several drugs have attracted attention as potential neuroprotective agents in PD. There are numerous studies demonstrating beneficial effects in the laboratory, but clinical efficacy for neuroprotection remains unproven.

摘要

帕金森病(PD)研究的一个主要重点是开发能够减缓或阻止临床进展的药物或其他干预措施。这应该包括对运动和非运动症状都有影响,从而针对多巴胺能和非多巴胺能途径。基于对 PD 的病因和发病机制有更好的理解,并确定关键的分子靶点,从而开发出此类疗法的可能性最大,这是合乎逻辑的假设。虽然已经在寻找 PD 的不同遗传原因和风险因素方面取得了重大进展,但在发现环境因素方面进展较少。单独的遗传原因仍然存在共同的细胞功能障碍和死亡途径,并且在多个层面上相互关联。尽管在遗传学和 PD 发病机制方面取得了重大进展,但我们仍然没有很好的 PD 模型,可以自信地用于准确预测药物对疾病进展的影响。临床试验设计和研究人群选择也是测试任何潜在神经保护剂的重要挑战领域。有几种药物作为 PD 的潜在神经保护剂引起了关注。有许多研究表明在实验室中具有有益的效果,但神经保护的临床疗效仍未得到证实。

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