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Abnormal processing of collapsin response mediator protein 2 (CRMP2) in Parkinson’s disease

Title
Abnormal processing of collapsin response mediator protein 2 (CRMP2) in Parkinson’s disease
Author
송재필
Alternative Author(s)
송재필
Advisor(s)
서혜명
Issue Date
2021. 2
Publisher
한양대학교
Degree
Master
Abstract
Parkinson's disease (PD) is the second most prevalent chronic neurodegenerative disorders. PD is caused by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta of the brain. Mutation in leucine-rich repeat kinase (LRRK2) is frequently found in both familial and sporadic PD. LRRK2 ras of complex domain R1441G mutation has been previously studied to explain dopaminergic cell death. In previous study, we determined differentially phosphorylated proteins in LRRK2 R1441G transgenic mice using phospho-proteomics technology and found that several cytoskeletal proteins are involved as phosphorylated targets including collapsin response mediator protein 2 (CRMP2). CRMPs have been reported as crucial regulator of microtubule dynamics during neurite/axonal growth. In this study, we determined that phosphorylation level of CRMP2 was increased in LRRK2 R1441G transgenic mice compared to normal mice. When GW5074 was administered to inhibit LRRK2 activity, the level of phosphorylation of CRMP2 was down-regulated in vivo and in vitro PD models. GW5074 also improved neurite outgrowth of primary cultured cells and improved motor deficits in LRRK2 R1441G mice. These results suggest that cytoskeletal proteins including CRMP2 are pathologically targeted in LRRK2 R1441G Parkinson's disease model and the phosphorylation of specific cytoskeletal protein can explain the mechanism of dysfunctional cytoskeletal transport in PD.
URI
https://repository.hanyang.ac.kr/handle/20.500.11754/159558http://hanyang.dcollection.net/common/orgView/200000485324
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > MOLECULAR & LIFE SCIENCE(분자생명과학과) > Theses (Master)
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