Methylation changes and aberrant expression of FGFR3 in Lewy body disease neurons
Methylation changes and aberrant expression of FGFR3 in Lewy body disease neurons
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DOI：
10.1016/j.brainres.2018.06.017
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发表时间：
2018-10
期刊：
影响因子：
2.9
通讯作者：
Takeyuki Tsuchida;T. Mano;Kagari Koshi-Mano;T. Bannai;T. Matsubara;S. Yamashita;T. Ushijima;K. Nagata;S. Murayama;T. Toda;S. Tsuji;A. Iwata
中科院分区：
文献类型：
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作者：
Takeyuki Tsuchida;T. Mano;Kagari Koshi-Mano;T. Bannai;T. Matsubara;S. Yamashita;T. Ushijima;K. Nagata;S. Murayama;T. Toda;S. Tsuji;A. Iwata
路易体病（Lewy body disease，LBD）是一种中枢神经系统内α-突触核蛋白聚集形成的嗜酸性胞浆包涵体，称为路易体。根据其分布方式可分为脑干LBD、边缘系统LBD和弥漫性新皮质LBD。据报道，α-突触核蛋白影响MAPK级联反应中的各个点，但其与FGF受体（该途径的最上游）的关系以前尚未研究。我们发现，在四种FGFR中，FGFR 3在LBD脑组织病理学中显示神经元上调。使用神经元特异性甲基化组分析的进一步检查显示，FGFR 3的基因体在LBD中被高甲基化，表明其转录增加。在非神经元基因组中未观察到改变的甲基化。改变的甲基化状态与α-突触核蛋白病理学的严重程度相关。
Lewy body disease (LBD) is characterized by accumulation of aggregated α-synuclein in the central nervous system as eosinophilic cytoplasmic inclusions called Lewy bodies. According to their distribution pattern, it is classified into brainstem LBD, limbic LBD and diffuse neocortical LBD. It has been reported that α-synuclein affects various points in the MAPK cascade but its relationship with FGF receptors, which are the most upstream of the pathway, has not been previously investigated. We discovered that among the four FGFRs, FGFR3 showed neuronal upregulation in LBD brains histopathologically. Further examination using neuron-specific methylome analysis revealed that the gene body of FGFR3 was hypermethylated in LBD, suggesting its increased transcription. Altered methylation was not observed in the non-neuronal genome. Altered methylation status was associated with the severity of α-synuclein pathology.