Korean Biological research group in Michigan

KBM은 미시간에서 의학, 약학, 생물학 관련 연구를 수행하는 연구자들간의 시너지를 도모하는 모임 입니다.

매달 학술 세미나 및 네트워킹 세션을 진행 하고 있으며, 미시간에 계시는 모든 연구자들의 참여를 환영합니다.

KBM is first organized by a group of researchers from the University of Michigan working in various bio-related fields. Since 2020, we have been having regular seminars and network sessions through an online platform. We believe now is the right timing for expanding our group beyond the Michigan area. So if you are interested in joining the seminars and meetings, please contact us!

Contact: kbm.president@gmail.com

Concentration of non-myocyte proteins in arterial media of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

l Abstract

The most common inherited cause of vascular dementia and stroke, cerebral autosomal dominant arteriopathy with subcortical infacts and leukoencephalopathy (CADASIL), is caused by mutations in NOTCH3. Post-translationally altered NOTCH3 accumulates in the vascular media of CADASIL arteries in areas of the vessels that exhibit profound cellular degeneration. The identification of molecules that concentrate in the same location as altered pathological NOTCH3 may shed light on process that drive cytopathology in CADASIL. We performed an immunohistochemical screen of markers identified in the Human Protein Atlas to identify new proteins that accumulate in the vascular media in a pattern similar to pathological NOTCH3. None of 16 smooth muscle cell markers exhibited NOTCH3-like patterns of expression, although several exhibited disease-dependent patterns of expression, with FAM124A, GZMM, MTFR1, and ST6GAL demonstrating higher expression in controls than CADASIL. In contrast, three non-smooth muscle proteins, CD63, CTSH, and IL17RC, localized to the same regions as pathological NOTCH3. Proximity ligation assays support complex formation between NOTCH3 fragments and CD63 in degenerating CADASIL media. The three novel CADASIL markers are preferentially expressed in perivascular cells in normal vessels, and mRNA encoding these molecules are expressed around the media in CADASIL. The identification of new proteins that concentrate in CADASIL vascular media demonstrates the utility of querying publicly available protein databases in specific neurological diseases and uncovers unexpected origins of vascular medial markers.