New synaptic and molecular targets for neuroprotection in Parkinson's disease.

New synaptic and molecular targets for neuroprotection in Parkinson's disease.
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DOI:
10.1002/mds.25096
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发表时间:
2013-01
期刊:
影响因子:
8.6
通讯作者:
Dawson, Ted M.
Dawson, Ted M.
中科院分区:
医学1区
文献类型:
--
作者:
Calabresi, Paolo;Di Filippo, Massimiliano;Gallina, Antongiulio;Wang, Yingfei;Stankowski, Jeannette N.;Picconi, Barbara;Dawson, Valina L.;Dawson, Ted M.

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帕金森病(PD)的主要解剖学特征是黑质致密部(SNc)神经元的变性,导致纹状体多巴胺(DA)缺乏,并随之改变基底神经节的生理机能。针对多巴胺能系统的治疗可以缓解PD症状,但不能减缓PD进展的神经退行性过程。纹状体核包括一个由突起神经元和中间神经元组成的复杂网络,这些神经元整合不同的神经信号来调节基底神经节回路的活动。在这篇综述中,我们描述了新的潜在的分子和突触纹状体靶点,以发展PD的症状和神经保护策略。我们特别关注腺苷A2A受体和多巴胺D2受体之间的相互作用,NMDA受体正确组装的作用,以及sGC/cGMP/PKG途径。此外,我们还讨论了靶向细胞死亡程序parthanatos和激酶LRRK2的可能性,以开发新的假定的PD神经保护剂,作用于多巴胺能神经元和其他基底神经节结构。
The defining anatomical feature of Parkinson’s disease (PD) is the degeneration of substantia nigra pars compacta (SNc) neurons, resulting in striatal dopamine (DA) deficiency and in the subsequent alteration of basal ganglia physiology. Treatments targeting the dopaminergic system alleviate PD symptoms but are not able to slow the neurodegenerative process that underlies PD progression. The nucleus striatum comprises a complex network of projecting neurons and interneurons that integrates different neural signals to modulate the activity of the basal ganglia circuitry. In this review we describe new potential molecular and synaptic striatal targets for the development of both symptomatic and neuroprotective strategies for PD. In particular, we focus on the interaction between adenosine A2A receptors and dopamine D2 receptors, on the role of a correct assembly of NMDA receptors, and on the sGC/cGMP/PKG pathway. Moreover, we also discuss the possibility to target the cell death program parthanatos and the kinase LRRK2 in order to develop new putative neuroprotective agents for PD acting on dopaminergic nigral neurons as well as on other basal ganglia structures.
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