File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
  • Find via Find It@HKUL

Conference Paper: Understanding molecular mechanisms in mitochondria underlying LRRK2-related Parkinson’s disease

TitleUnderstanding molecular mechanisms in mitochondria underlying LRRK2-related Parkinson’s disease
Authors
Issue Date2010
PublisherFederation of American Societies for Experimental Biology. Meeting abstracts can be accessed via http://www.fasebj.org/search.dtl
Citation
The 2010 Annual Meeting of Experimental Biology (EB), Anaheim, CA., 24-28 April 2010. In FASEB Journal, 2010, v. 24 meeting abstracts, abstract no. 891.3 How to Cite?
AbstractParkinson’s disease (PD) is a common neurodegenerative movement disorder. Mutation of LRRK2 is pathogenic in PD. So far, more than 20 mutations of LRRK2 have been reported in Parkinson patients of different races. Some of the mutations were shown to be able to increase. We aim to elucidate the importance of LRRK2 in the pathogenesis of PD by studying the effects of this protein on vulnerability of neuronal cell death under oxidative stress. MATERIALS AND METHODS: We have developed stable HEK293 cells overexpressing wild-type and mutated (R1441G, G2019S) LRRK2. The effects of LRRK2 over-expression on various mitochondrial parameters were determined, e.g. cell viability, mitochondrial complexes (I–IV) activity and membrane potential, ATP/ADP ratio, and mitochondrial fragmentation after challenged with H2O2 to induce oxidative stress. We generated R1441G LRRK2 knockin (KI) mice. We are characterizing the LRRK2 R1441G KI mice and wildtype mice by immunohistochemistry of tyrosine hydroxylase (TH) to identify TH+ neurons after challenged with MPTP injection (IP) for 2 weeks to induce nigrostriatal degeneration. RESULTS: Our preliminary data showed that the intracellular expression pattern of mutant LRRK2 (G2019S) in HEK293 was different from the wild-type under oxidative stress by H2O2. Mutant LRRK2 was translocated towards mitochondria after treatment with H2O2. LDH release and ATP/ADP ratio proved more serious trend of apoptosis in mutant LRRK2 cell lines. Mitochondrial complexes I activity and mitochondrial fragmentation level were also changed between wild type and single mutation proteins (R1441G and G2019S) in HEK293. The results of this study have important implication on understanding the mitochondrial dysfunction in the pathogenesis of PD.
DescriptionPoster session - Biochemistry and Molecular Biology: abstract no. 891.3
Persistent Identifierhttp://hdl.handle.net/10722/160163
ISSN
2015 Impact Factor: 5.299
2015 SCImago Journal Rankings: 2.775

 

DC FieldValueLanguage
dc.contributor.authorLiu, Hen_US
dc.contributor.authorHo, WLen_US
dc.contributor.authorHo, WMen_US
dc.contributor.authorZhou, ZJen_US
dc.contributor.authorHo, SLen_US
dc.date.accessioned2012-08-16T06:05:18Z-
dc.date.available2012-08-16T06:05:18Z-
dc.date.issued2010en_US
dc.identifier.citationThe 2010 Annual Meeting of Experimental Biology (EB), Anaheim, CA., 24-28 April 2010. In FASEB Journal, 2010, v. 24 meeting abstracts, abstract no. 891.3en_US
dc.identifier.issn0892-6638-
dc.identifier.urihttp://hdl.handle.net/10722/160163-
dc.descriptionPoster session - Biochemistry and Molecular Biology: abstract no. 891.3-
dc.description.abstractParkinson’s disease (PD) is a common neurodegenerative movement disorder. Mutation of LRRK2 is pathogenic in PD. So far, more than 20 mutations of LRRK2 have been reported in Parkinson patients of different races. Some of the mutations were shown to be able to increase. We aim to elucidate the importance of LRRK2 in the pathogenesis of PD by studying the effects of this protein on vulnerability of neuronal cell death under oxidative stress. MATERIALS AND METHODS: We have developed stable HEK293 cells overexpressing wild-type and mutated (R1441G, G2019S) LRRK2. The effects of LRRK2 over-expression on various mitochondrial parameters were determined, e.g. cell viability, mitochondrial complexes (I–IV) activity and membrane potential, ATP/ADP ratio, and mitochondrial fragmentation after challenged with H2O2 to induce oxidative stress. We generated R1441G LRRK2 knockin (KI) mice. We are characterizing the LRRK2 R1441G KI mice and wildtype mice by immunohistochemistry of tyrosine hydroxylase (TH) to identify TH+ neurons after challenged with MPTP injection (IP) for 2 weeks to induce nigrostriatal degeneration. RESULTS: Our preliminary data showed that the intracellular expression pattern of mutant LRRK2 (G2019S) in HEK293 was different from the wild-type under oxidative stress by H2O2. Mutant LRRK2 was translocated towards mitochondria after treatment with H2O2. LDH release and ATP/ADP ratio proved more serious trend of apoptosis in mutant LRRK2 cell lines. Mitochondrial complexes I activity and mitochondrial fragmentation level were also changed between wild type and single mutation proteins (R1441G and G2019S) in HEK293. The results of this study have important implication on understanding the mitochondrial dysfunction in the pathogenesis of PD.-
dc.languageengen_US
dc.publisherFederation of American Societies for Experimental Biology. Meeting abstracts can be accessed via http://www.fasebj.org/search.dtl-
dc.relation.ispartofFASEB Journalen_US
dc.titleUnderstanding molecular mechanisms in mitochondria underlying LRRK2-related Parkinson’s diseaseen_US
dc.typeConference_Paperen_US
dc.identifier.emailLiu, H: liuhf@hku.hken_US
dc.identifier.emailHo, WL: hwl2002@hku.hken_US
dc.identifier.emailZhang, W: zhang833@hku.hken_US
dc.identifier.emailHo, WM: seeka@hku.hken_US
dc.identifier.emailZhou, Z: zhongjun@hkucc.hku.hken_US
dc.identifier.emailHo, SL: slho@hku.hken_US
dc.identifier.authorityHo, WL=rp00259en_US
dc.identifier.authorityZhou, ZJ=rp00503en_US
dc.identifier.authorityHo, SL=rp00240en_US
dc.identifier.hkuros204225en_US
dc.identifier.volume24-
dc.identifier.issuemeeting abstracts-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats