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Effects of LRRK2 genetic mutations on mitochondrial function in Parkinson's disease model mice

Title
Effects of LRRK2 genetic mutations on mitochondrial function in Parkinson's disease model mice
Other Titles
파킨슨씨병 모델 생쥐에서 LRRK2 유전자 돌연변이가 미토콘드리아 기능에 미치는 영향
Author
김주의
Alternative Author(s)
김주의
Advisor(s)
서혜명
Issue Date
2015-02
Publisher
한양대학교
Degree
Master
Abstract
Parkinson’s disease (PD) is progressive and complex neurodegenerative brain disorder that results in degeneration of nigrostriatal dopaminergic neurons. PD is caused by a number of factors, including genetic mutations, oxidative stress, mitochondrial abnormalities, and aging, etc. Mutation of leucine-rich repeat kinase 2 (LRRK2) which contain GTPase and kinase domain is one of the most popular genetic cause of PD. To identify the progressive changes of mitochondrial dynamics by aging in LRRK2 G2019S and LRRK2 R1441G mutation, we used LRRK2 G2019S and LRRK2 R1441G mice which showed significantly worse performance in rotatod test at over 11 month of age. We determined that mitochondria complex Ⅱ/Ⅲ activity were decreased by mutation in group of LRRK2 R1441G mice at the 8 and 20 months of age. The cellular ATP levels were decreased at the 1 month of age in the striatum of LRRK2 R1441G mice. We determined the expression level of Mitochondria fission 2(MFN2), mitochondria fission-fusion related genes, was decreased in the striatum of LRRK2 G2019S mice by mutation. The mRNA expression level of MFN1 is decreased in R1441G mice over 8 months of age by aging. Our results suggest that the LRRK2 G2019S and R1441G mutation and aging affect to the mitochondrial dynamics. Mitochondrial dynamics can be applied for future therapeutics for PD.
URI
https://repository.hanyang.ac.kr/handle/20.500.11754/129355http://hanyang.dcollection.net/common/orgView/200000425745
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > MOLECULAR & LIFE SCIENCE(분자생명과학과) > Theses (Master)
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