Uemura Masahiro, Nozaki Hiroaki, Onodera Osamu
Department of Neurology, Clinical Neuroscience Branch, Brain Research Institute, Niigata University.
Brain Nerve. 2017 Jan;69(1):25-33. doi: 10.11477/mf.1416200631.
Cerebral small vessel disease (CSVD) is frequently observed among the elderly and is known to cause dementia and gait disturbance associated with white matter lesions, lacunar infarcts, and cerebral hemorrhage. Molecular mechanistic studies promise to provide new insights into the pathogenesis of hereditary CSVD. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is one of the hereditary CSVDs caused by a mutation in the high-temperature requirement serine peptidase A1 (HTRA1) gene. The loss of HTRA1 protease activity increases signaling via transforming growth factor (TGF)β, thereby resulting in CARASIL. Although the CARASIL has been characterized by juvenile onset alopecia and spondylosis deformans, these features are not always observed in individuals with an HTRA1 mutation. Moreover, some HTRA1 mutations cause CSVD in heterozygous states. Therefore, the clinical features of CSVD resulting from an HTRA1 mutation extend to patients with CSVD alone or to those with dominantly inherited CSVD.
脑小血管病（CSVD）在老年人中很常见，已知会导致与白质病变、腔隙性梗死和脑出血相关的痴呆和步态障碍。分子机制研究有望为遗传性CSVD的发病机制提供新的见解。伴有皮质下梗死和白质脑病的脑常染色体隐性动脉病（CARASIL）是由高温需求丝氨酸蛋白酶A1（HTRA1）基因突变引起的遗传性CSVD之一。HTRA1蛋白酶活性的丧失会增加通过转化生长因子（TGF）β的信号传导，从而导致CARASIL。尽管CARASIL的特征是青少年期脱发和脊柱关节病，但这些特征在HTRA1突变个体中并不总是出现。此外，一些HTRA1突变会在杂合状态下导致CSVD。因此，由HTRA1突变引起的CSVD的临床特征延伸至仅患有CSVD的患者或患有显性遗传CSVD的患者。
