biostudies-literatureUnknown10Uemura MTakeda Science FoundationJapan Agency for Medical Research and DevelopmentMinistry of Education, Culture, Sports, Science and Technology<b>Background:</b> Mutations in the <i>high-temperature requirement A serine peptidase 1 (HTRA1)</i> cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Most carriers for <i>HTRA1</i> mutations are asymptomatic, but more than 10 mutations have been reported in symptomatic carriers. The molecular differences between the mutations identified in symptomatic carriers and mutations identified only in CARASIL patients are unclear. HTRA1 is a serine protease that forms homotrimers, with each HTRA1 subunit activating the adjacent HTRA1 via the sensor domain of loop 3 (L3) and the activation domain of loop D (LD). Previously, we analyzed four HTRA1 mutant proteins identified in symptomatic carriers and found that they were unable to form trimFrontiers in neurology693https://www.ebi.ac.uk/biostudies/studies/S-EPMC6611441biostudies-literatureHTRA1 Mutations Identified in Symptomatic Carriers Have the Property of Interfering the Trimer-Dependent Activation Cascade.PMC6611441Koyama AAndo SOnodera ONozaki HKanazawa MUemura MKato TSakai NfalseHTRA1 Mutations Identified in Symptomatic Carriers Have the Property of Interfering the Trimer-Dependent Activation Cascade.<b>Background:</b> Mutations in the <i>high-temperature requirement A serine peptidase 1 (HTRA1)</i> cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Most carriers for <i>HTRA1</i> mutations are asymptomatic, but more than 10 mutations have been reported in symptomatic carriers. The molecular differences between the mutations identified in symptomatic carriers and mutations identified only in CARASIL patients are unclear. HTRA1 is a serine protease that forms homotrimers, with each HTRA1 subunit activating the adjacent HTRA1 via the sensor domain of loop 3 (L3) and the activation domain of loop D (LD). Previously, we analyzed four HTRA1 mutant proteins identified in symptomatic carriers and found that they were unable to form trim2019-01-01T00:00:00Z20192025-04-26T19:16:23.601Z2019-07-25T07:05:04ZS-EPMC66114413131645810.3389/fneur.2019.00693