α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy?
α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy?
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DOI：
10.1007/s00401-013-1096-7
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发表时间：
2013-05
影响因子：
12.7
通讯作者：
Holton JL
中科院分区：
文献类型：
--
作者：
Kiely AP;Asi YT;Kara E;Limousin P;Ling H;Lewis P;Proukakis C;Quinn N;Lees AJ;Hardy J;Revesz T;Houlden H;Holton JL
我们报告了一个年轻发病的帕金森氏病(PD)英国家庭，G51D SNCA突变与该疾病分离。家族史与常染色体显性遗传是一致的，因为先证者的父亲和妹妹都患上了左旋多巴反应性帕金森综合症，发病时间为他们近30岁。临床表现与SNCA三倍体家系相似，与A53T SNCA突变病例相似。对先证者的尸检发现，除尾状核、壳核、苍白球和杏仁核外，额叶和颞叶也有萎缩。黑质和蓝斑的色素沉着严重消失。神经元丢失以额叶和颞叶皮质、海马CA2/3区、黑质、蓝斑和迷走神经背侧运动核最为明显。细胞病理学表现为广泛而频繁的神经元α-突触核蛋白免疫反应包涵体，形态多样，少突胶质包涵体类似于多系统萎缩的胶质细胞质包涵体。这两种包涵体类型均为泛素和p62阳性，并被磷酸化依赖的抗α-突触核蛋白抗体标记。此外，在边缘区域和纹状体内观察到TDP43免疫反应阳性包涵体。总之，这些数据显示出与A53T SNCA突变和倍增病例的临床和神经病理学相似之处。此病例的细胞神经病理特征具有PD和MSA的一些特征，另外还有独特的纹状体和新皮质病理。进一步了解G51D突变的致病机制有助于理解α-突触核蛋白生物学及其对疾病表型的影响。本文的在线版本(doi：10.1007/s00401-0131096-7)包含补充材料，授权用户可以使用。
We report a British family with young-onset Parkinson’s disease (PD) and a G51D SNCA mutation that segregates with the disease. Family history was consistent with autosomal dominant inheritance as both the father and sister of the proband developed levodopa-responsive parkinsonism with onset in their late thirties. Clinical features show similarity to those seen in families with SNCA triplication and to cases of A53T SNCA mutation. Post-mortem brain examination of the proband revealed atrophy affecting frontal and temporal lobes in addition to the caudate, putamen, globus pallidus and amygdala. There was severe loss of pigmentation in the substantia nigra and pallor of the locus coeruleus. Neuronal loss was most marked in frontal and temporal cortices, hippocampal CA2/3 subregions, substantia nigra, locus coeruleus and dorsal motor nucleus of the vagus. The cellular pathology included widespread and frequent neuronal α-synuclein immunoreactive inclusions of variable morphology and oligodendroglial inclusions similar to the glial cytoplasmic inclusions of multiple system atrophy (MSA). Both inclusion types were ubiquitin and p62 positive and were labelled with phosphorylation-dependent anti-α-synuclein antibodies In addition, TDP-43 immunoreactive inclusions were observed in limbic regions and in the striatum. Together the data show clinical and neuropathological similarities to both the A53T SNCA mutation and multiplication cases. The cellular neuropathological features of this case share some characteristics of both PD and MSA with additional unique striatal and neocortical pathology. Greater understanding of the disease mechanism underlying the G51D mutation could aid in understanding of α-synuclein biology and its impact on disease phenotype. The online version of this article (doi:10.1007/s00401-013-1096-7) contains supplementary material, which is available to authorized users.
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影响因子：
15
作者：
Hejjaoui, Mirva;Butterfield, Sara;Fauvet, Bruno;Vercruysse, Filip;Cui, Jia;Dikiy, Igor;Prudent, Michel;Olschewski, Diana;Zhang, Yan;Eliezer, David;Lashuel, Hilal A.
通讯作者：
Lashuel, Hilal A.
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：
12.7
作者：
Brandmeir, Nicholas J.;Geser, Felix;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
15.9
作者：
Chen, Li;Periquet, Magali;Feany, Mel B.
通讯作者：
Feany, Mel B.
DOI：
10.1523/jneurosci.0490-10.2010
发表时间：
2010-05-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Clinton LK;Blurton-Jones M;Myczek K;Trojanowski JQ;LaFerla FM
通讯作者：
LaFerla FM