Molecular pathogenesis of cerebral small vessel disease.

脑血管病是老年人的常见病；然而，其分子基础尚不清楚。我们最近证明，高温需求A （HTRA）丝氨酸肽酶1 （HTRA1）基因突变可导致遗传性脑小血管疾病、脑常染色体隐性动脉病伴皮层下梗死和脑白质病（CARASIL）。HTRA1属于HTRA蛋白家族，该家族成员具有伴侣蛋白和丝氨酸蛋白酶的双重活性，并抑制转化生长因子- β (tgf - β)家族信号传导。我们研究了HTRA1缺失小鼠CARASIL的分子发病机制。免疫组化分析发现模型脑小血管有明显改变。该模型小鼠可为研究脑血管病的发病机制提供参考。

Cerebral small-vessel disease is a common disorder in elderly populations; however, its molecular basis is not well understood. We recently demonstrated that mutations in the high-temperature requirement A (HTRA) serine peptidase 1 (HTRA1) gene cause a hereditary cerebral small-vessel disease, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). HTRA1 belongs to the HTRA protein family, whose members have dual activities as chaperones and serine proteases and also repress transforming growth factor-beta (TGF-beta) family signaling. We investigated the molecular pathogenesis of CARASIL in HTRA1 null mouse. By immunohistochemical analysis we have found the alteration in cerebral small vessels in the model. This model mouse could be useful for the investigation of the pathogenesis of cerebral small vessel disease.