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  • 03월 10일 13시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

대한화학회 제105회 학술발표회 및 총회 Role of ubiquitin in neuroprotection

2010년 2월 22일 15시 18분 01초
금13C2심 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
금 09시 : 55분
생명화학 - 단백질 과학의 생화학적 접근
저자 및
서울시립대학교 생명과학과, Korea
Pathogenesis of neurodegenerative diseases, such as Alzheimer’s and Huntington’s diseases, is linked to the accumulation of non-native protein aggregates or inclusion bodies, which are pathological hallmarks of these disorders. In addition, abnormal accumulations of ubiquitin (Ub) within neuronal inclusion bodies have been diagnostic features of nearly all neurodegenerative diseases. Although it is clear that these diseases are associated with the accumulation of ubiquitinated aggregates, it has not been extensively studied how it leads to neuronal loss or dysfunction. Our hypothesis is that the formation of ubiquitinated aggregates disrupts Ub pool dynamics by shifting the Ub pool equilibrium towards Ub conjugates and reducing the availability of free Ub, which is associated with diverse neurological disorders. In our previous study, we have demonstrated that modest depletion of cellular Ub is sufficient to cause neuronal dysfunction and neurodegeneration. Therefore, the goal of this project is to identify the role of Ub in regulating neuronal function and survival. To this end, we determined the spatial profiles of polyubiquitin gene (Ubb and Ubc) expression patterns and their contribution to total Ub levels in mouse brain under normal and stressed conditions. Next, we will determine whether free Ub levels are reduced and Ub pool dynamics are disrupted in the affected brain regions where inclusion bodies are formed using selected aging-related mouse models of neurodegeneration, and we will rescue neuropathological lesions by providing extra free Ub via lentiviral-mediated delivery. This will directly prove the neuroprotective role of Ub and eventually identify underlying molecular mechanisms why Ub deficiency in neurons causes neuronal loss or dysfunction leading to various neurological disorders. This work is supported by a grant from the Korea Health Industry Development Institute (A084520).