Brain and nerve = Shinkei kenkyū no shinpo
-
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a single-gene disorder directly affecting the cerebral small blood vessels, that is caused by mutations in the HTRA1 gene encoding HtrA serine peptidase/protease 1 (HTRA1). CARASIL is the second known genetic form of ischemic, nonhypertensive, cerebral small-vessel diseases with an identified gene, following CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). The exact prevalence of CARASIL is currently unknown, and so far about 50 patients have been reported, most of them from Japan and two from China. ⋯ CARASIL is a prototype single-gene disorder of cerebral small vessels, secondary to and distinct from CADASIL. CARASIL-associated mutant HTRA1s exhibited decreased protease activity and failed to repress transforming growth factor-β (TGF-β) family signaling, indicating that the increased TGF-β signaling causes arteriopathy in CARASIL. Therefore, HTRA1 represents another new gene to be considered in future studies of the mechanisms and therapeutic strategies of cerebral small-vessel diseases, as well as alopecia and degenerative vertebral/disk diseases.