Mizuno Toshiki, Mizuta Ikuko, Watanabe-Hosomi Akiko, Mukai Mao, Koizumi Takashi
Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Front Aging Neurosci. 2020 May 7;12:91. doi: 10.3389/fnagi.2020.00091. eCollection 2020.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebral small vessel disease caused by mutations in , is characterized by recurrent stroke without vascular risk factors, mood disturbances, and dementia. MRI imaging shows cerebral white matter (WM) hyperintensity, particularly in the external capsule and temporal pole. Missense mutations related to a cysteine residue in the 34 EGFr on the NOTCH3 extracellular domain (N3ECD) are a typical mutation of CADASIL. On the other hand, atypical mutations including cysteine sparing mutation, null mutation, homozygous mutation, and other associate genes are also reported. From the viewpoint of gain of function apart from Notch signaling or loss of function of Notch signaling, we review the research article about CADASIL and summarized the pathogenesis of small vessel, stroke, and dementia in this disease.
伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）是一种由 突变引起的遗传性脑小血管疾病，其特征为无血管危险因素的复发性中风、情绪障碍和痴呆。MRI 成像显示脑白质（WM）高信号，尤其是在壳核外和颞极。NOTCH3 细胞外结构域（N3ECD）上与 34 个表皮生长因子受体（EGFr）中的半胱氨酸残基相关的错义突变是 CADASIL 的典型突变。另一方面，也报道了包括半胱氨酸保留突变、无效突变、纯合突变和其他相关基因在内的非典型突变。从Notch信号功能获得或Notch信号功能丧失的角度，我们回顾了关于CADASIL的研究文章，并总结了该疾病中小血管、中风和痴呆的发病机制。 （注：原文中“in ”处信息缺失，译文根据已有内容尽量完整翻译）
