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Studies on the role of phosphorylation of alpha-synuclein in alpha-synuclein degradation pathway
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 김용식 | - |
dc.contributor.author | 최희순 | - |
dc.date.accessioned | 2017-07-14T01:24:30Z | - |
dc.date.available | 2017-07-14T01:24:30Z | - |
dc.date.issued | 2013-08 | - |
dc.identifier.other | 000000012931 | - |
dc.identifier.uri | https://hdl.handle.net/10371/121923 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 의학과 약리학 전공, 2013. 8. 김용식. | - |
dc.description.abstract | α-Synuclein (α-SYN) has been characterized as a heat-stable and aggregation-prone protein that can be degraded by both the ubiquitin-proteasomal pathway and the chaperone-lysosomal pathway. However, the switching mechanism between the two pathways is not well understood. In my study, I investigated the increase of the binding of α-SYN to heat shock protein 70 cognate (HSC70) and the lysosomal translocation of α-SYN. Tyrosine phosphorylation at Y136 of α-SYN increased its binding to HSC70. I also found that Y136 phosphorylation of α-SYN can be regulated by the focal adhesion kinase pp125 (FAK) and protein tyrosine phosphatase 1B (PTP1B). Furthermore, a PTP1B inhibitor prevented the accumulation of α-SYN in SH-SY5Y cells by increasing α-SYN translocation into the lysosome, protected dopaminergic neurons against cell death and rescued Rotarod performance in a Parkinsons disease (PD) model. I provide evidence that the regulation of the phosphorylation of α-SYN at Y136 can improve behavioral performance and protect dopaminergic neurons against cell death through enhanced lysosomal degradation of α-SYN. | - |
dc.description.tableofcontents | Abstract in English i
Contents iii List of Figures iv List of Abbreviations vi Introduction 1 Materials and Methods 5 Results 12 Discussion 44 References 49 Abstract in Korean 58 | - |
dc.format | application/pdf | - |
dc.format.extent | 4020590 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | α-synuclein | - |
dc.subject | proteasome | - |
dc.subject | lysosome | - |
dc.subject | tyrosine | - |
dc.subject | Parkinson’s disease | - |
dc.subject | phosphorylation | - |
dc.subject.ddc | 610 | - |
dc.title | Studies on the role of phosphorylation of alpha-synuclein in alpha-synuclein degradation pathway | - |
dc.type | Thesis | - |
dc.description.degree | Doctor | - |
dc.citation.pages | vii, 59 | - |
dc.contributor.affiliation | 의과대학 의학과 | - |
dc.date.awarded | 2013-08 | - |
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