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The role of local translation in axon survival induced by wldS and sarm1

Other Titles
 wlds와 sarm1에 의한 축삭 생존에서 국소적인 단백질 번역의 역할 
Authors
 장정임 
Degree
석사
Issue Date
2017
Description
의과학
Abstract
Neurons are connected to each other via their axons, and maintaining these structures is necessary for normal brain functions. Failure to maintain axonal integrity is closely linked to most neurodegenerative diseases. Therefore, understanding how axon survival is regulated is key to understand brain function and diseases. Wallerian degeneration, fragmentation of distal axons severed from their cell bodies, shares molecular and cellular characteristics with disease-associated axon degeneration, and therefore is widely used as a model to study axon survival and degeneration. Genetic studies in mouse and fly revealed unexpectedly that axon degeneration is an active process, conceptually akin to compartmentalized apoptosis, which requires axon destruction gene, sarm1. Sarm1 null mouse and fly exhibit delayed Wallerian degeneration, and it is believed that sarm1 promotes axon degeneration by counteracting axon survival nmnat genes. Wallerian degeneration slow (wldS), a gain-of-function mutant form of nmnat1, also delays Wallerian degeneration. However, how these genes regulate axon survival and degeneration remains unclear, particularly how severed axons survive for weeks. Based on recent studies showing that axonal protein synthesis is required for axon survival and maintenance, this thesis investigates the hypothesis that local translation is required for Wallerian degeneration-resisting distal axons to survive. Using the visual system of Xenopus tropicalis as a model, I show that functions of wldS and sarm1 are conserved in Xenopus, and that cycloheximide treatment increases degeneration of these axons. These results provide direct evidence for the importance of local translation to maintain normal structure in Wallerian degeneration-resisting axons and insight into how survival might be regulated in vivo.
Files in This Item:
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Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 2. Thesis
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/167863
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