Expression of α-synuclein is regulated in a neuronal cell type-dependent manner.
Expression of α-synuclein is regulated in a neuronal cell type-dependent manner.
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DOI：
10.1007/s12565-018-0464-8
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发表时间：
2019-01
影响因子：
1.2
通讯作者：
Tanaka M
中科院分区：
文献类型：
--
作者：
Taguchi K;Watanabe Y;Tsujimura A;Tanaka M
α-突触核蛋白（α-Synuclein）是路易体（Lewy bodies，LB）和路易神经突（Lewy neurites，LN）的主要成分，在正常生理条件下表达于突触前，参与突触功能。错误折叠的α-突触核蛋白如LB和LN的异常细胞内聚集体是突触核蛋白病（包括帕金森病（PD）和路易体痴呆（DLB））的病理学标志。根据先前使用过表达α-突触核蛋白的病理模型的研究，神经元中该蛋白的高表达是神经变性的关键风险因素。因此，了解α-突触核蛋白在每种神经元细胞类型中的内源性表达水平是重要的。我们先前报道了α-突触核蛋白在体外和体内的差异表达谱。在野生型小鼠脑中，特别是在特发性PD进展期间受影响的易损区域中，α-突触核蛋白在一些早期PD受影响区域的神经元细胞体中高度表达，例如嗅球、迷走神经背侧运动核和黑质延髓部。α-突触核蛋白的突触表达主要伴随着囊泡谷氨酸转运蛋白-1（一种兴奋性突触标记蛋白）的表达。相比之下，抑制性突触中α-突触核蛋白的表达在不同的脑区中是不同的。最近的证据表明α-synuclein的差异表达谱与某些神经元群体的选择性脆弱性之间存在密切关系。对α-synuclein表达调控的进一步研究将有助于理解LB的病理机制，并为预防PD和DLB的发生提供新的治疗策略。
α-Synuclein, the major component of Lewy bodies (LBs) and Lewy neurites (LNs), is expressed in presynapses under physiologically normal conditions and is involved in synaptic function. Abnormal intracellular aggregates of misfolded α-synuclein such as LBs and LNs are pathological hallmarks of synucleinopathies, including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). According to previous studies using pathological models overexpressing α-synuclein, high expression of this protein in neurons is a critical risk factor for neurodegeneration. Therefore, it is important to know the endogenous expression levels of α-synuclein in each neuronal cell type. We previously reported differential expression profiles of α-synuclein in vitro and in vivo. In the wild-type mouse brain, particularly in vulnerable regions affected during the progression of idiopathic PD, α-synuclein is highly expressed in neuronal cell bodies of some early PD-affected regions, such as the olfactory bulb, the dorsal motor nucleus of the vagus, and the substantia nigra pars compacta. Synaptic expression of α-synuclein is mostly accompanied by expression of vesicular glutamate transporter-1, an excitatory synapse marker protein. In contrast, α-synuclein expression in inhibitory synapses differs among brain regions. Recently accumulated evidence indicates the close relationship between differential expression profiles of α-synuclein and selective vulnerability of certain neuronal populations. Further studies on the regulation of α-synuclein expression will help to understand the mechanism of LB pathology and provide an innovative therapeutic strategy to prevent PD and DLB onset.
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影响因子：
168.9
作者：
Chartier-Harlin, MC;Kachergus, J;Destée, A
通讯作者：
Destée, A
影响因子：
3.3
作者：
Li, JY;Jensen, PH;Dahlström, A
通讯作者：
Dahlström, A
影响因子：
4.8
作者：
Dermentzaki, Georgia;Paschalidis, Nikolaos;Stefanis, Leonidas
通讯作者：
Stefanis, Leonidas
DOI：
10.1126/science.1227157
发表时间：
2012-11-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Luk KC;Kehm V;Carroll J;Zhang B;O'Brien P;Trojanowski JQ;Lee VM
通讯作者：
Lee VM
影响因子：
2.9
作者：
Mori, F;Tanji, K;Wakabayashi, K
通讯作者：
Wakabayashi, K