mGluR4-positive allosteric modulation as potential treatment for Parkinson's disease.
mGluR4-positive allosteric modulation as potential treatment for Parkinson's disease.
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DOI：
10.4155/fmc.09.38
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发表时间：
2009-06
影响因子：
4.2
通讯作者：
Niswender CM
中科院分区：
文献类型：
--
作者：
Hopkins CR;Lindsley CW;Niswender CM
尽管帕金森病在近200年前首次被诊断出来，但对于大多数被诊断出的人来说，其有效治疗仍然是难以捉摸的。大多数患者的治疗金标准是3，4-二羟基-L-苯丙氨酸。这种药物适用于大多数疾病早期的个体;然而，经过几年的治疗后，耐药症状开始出现。人们越来越有兴趣寻找新的疗法来帮助帕金森病患者。这种策略不仅可以治疗疾病的症状问题，而且还可以保护多巴胺能神经元免于进一步退化。其中一个现在受到科学界广泛关注的靶点是代谢型谷氨酸受体mGluR 4。在这篇文章中，我们简要回顾帕金森病，然后最近的工作在mGluR领域，重点是努力寻找和优化新的mGluR 4正变构调节剂（PAM）。临床前在啮齿动物模型中，mGluR 4激活作为帕金森病的新治疗方法提供了很大的希望。此外，在正构谷氨酸位点特异性使用PAM而不是直接作用的激动剂，继续被验证为该靶点的可行治疗选择。预计这一领域的持续进展将进一步加深我们对mGluR 4调节作为帕金森病的新型对症和潜在疾病改善治疗的潜力的理解。
Although Parkinson’s disease was first diagnosed nearly 200 years ago, its effective treatment still remains elusive for most of those diagnosed. The gold standard of treatment for most patients is 3,4-dihydroxy-l-phenylalanine. This drug works for most individuals early in the disease; however, resistant symptoms start to emerge after several years of treatment. There has been increased interest in finding novel therapies to help Parkinson’s disease patients. Such strategies may have the benefit of not only treating the symptomatic issues of the disorder, but might also offer promise in protecting dopaminergic neurons from further degeneration. One such target that is now receiving much attention from the scientific community is the metabotropic glutamate receptor mGluR4. In this article, we briefly review Parkinson’s disease and then recent work in the mGluR area, with a focus on the efforts being made toward finding and optimizing novel mGluR4 positive allosteric modulators (PAMs). Preclinically in rodent models, mGluR4 activation has offered much promise as a novel treatment of Parkinson’s disease. Additionally, the specific use of PAMs, rather than direct-acting agonists at the orthosteric glutamate site, continues to be validated as a viable treatment option for this target. It is anticipated that continued progress in this area will further our understanding of the potential of mGluR4 modulation as a novel symptomatic and potentially disease-modifying treatment for Parkinson’s disease.
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影响因子：
7.3
作者：
Gillespie, Roger J.;Bamford, Samantha J.;Weiss, Scott M.
通讯作者：
Weiss, Scott M.
DOI：
10.1038/nrd2760
发表时间：
2009-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.3
作者：
Corti, C;Aldegheri, L;Ferraguti, F
通讯作者：
Ferraguti, F
影响因子：
2.7
作者：
Annoura, H;Fukunaga, A;Horikawa, Y
通讯作者：
Horikawa, Y
影响因子：
5.3
作者：
Canudas, AM;Di Giorgi-Gerevini, V;Melchiorri, D
通讯作者：
Melchiorri, D