講演情報
[S4-5]遺伝子解析が解き明かす脳小血管病病態
○小野寺 理 (新潟大学 脳研究所 脳神経内科)
Special functions of the brain are maintained by cerebral small vessels. In recent years, there has been much interest in the aging of cerebral small blood vessels. The stiffening of the vascular wall impairs the important function of cerebral small vessels in redistributing blood flow in a neural activity-dependent manner. The phenotype of this disease group is thought to be cerebral small vessel disease with white matter damage. Large-scale association analyses have isolated multiple loci involved in this condition. These includes genes associated with the extracellular matrix. These include HTRA1, the gene responsible for hereditary cerebral small vessel disease. HTRA1 was initially isolated as a causative gene for recessive hereditary cerebral small vessel disease. However, it was shown that heterozygotes also cause cerebral small vessel disease. It is presumed that the risk of cerebral small vessel disease increases with less residual activity of HTRA1 as a protease. HTRA1 substrates a wide range of proteins, including extracellular substrates. It is important to note that extracellular matrix disruption has been extracted as common pathogenesis of both non-hereditary cerebral small vessel diseases with white matter damage and hereditary cerebral small vessel diseases. In this presentation, we will discuss the perturbation of the extracellular matrix, which has been elucidated in a mouse model of HTRA1 gene abnormality, from the viewpoint of vascular aging.