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Rajsi Thaker Thesis.pdf (1.94 MB)

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Potential drug treatment for Duchenne muscular dystrophy which could be through upregulation of lipin1

Thaker, Rajsi Y.
http://orcid.org/0000-0001-5772-6185
http://rave.ohiolink.edu/etdc/view?acc_num=wright1629996330644397

Abstract Details

2021, Master of Science (MS), Wright State University, Biochemistry and Molecular Biology.
Duchenne muscular dystrophy (DMD) is a genetic disorder leading to progressive muscle degeneration and weakness due to mutation in dystrophin gene, which is very important for maintaining muscle membrane integrity. Dystrophin is the largest gene in the human genome therefore more prone to mutation. There is currently no cure for DMD. Our lab recently found that Lipin1 deficient myofibers showed upregulation of necroptosis correlated with the loss of muscle membrane integrity. Our primary approach for ameliorating dystrophic phenotype in DMD is through reduction of necroptosis using drugs which can potentially upregulate Lipin1 expression. In this study, we identified two drugs i.e., dexamethasone which is a glucocorticoid and rosiglitazone which is PPARĪ³ agonist, can elevate Lipin1 mRNA and protein expression levels in vivo and in vitro. Mdx mice treated with dexamethasone for two weeks and rosiglitazone for one week had elevated Lipin1 expression level and downregulated necroptotic markers including RIPK1, RIPK3, and MLKL. Rosiglitazone treatment in mdx mice also downregulated apoptotic markers including BAX, BAK and cleaved caspase-3. Our future study will identify whether the effects of dexamethasone and rosiglitazone on the inhibition of necroptotic markers and the improvement of membrane integrity of dystrophic muscles are through the upregulation of Lipin1 expression.
Hongmei Ren, Ph.D. (Advisor)
Weiwen Long, Ph.D. (Committee Member)
Michael Leffak, Ph.D. (Committee Member)
96 p.
Biochemistry; Molecular Biology
lipin1; dmd; necroptosis; apoptosis; dexamethasone; rosiglitazone

Recommended Citations

Citations

  • Thaker, R. Y. (2021). Potential drug treatment for Duchenne muscular dystrophy which could be through upregulation of lipin1 [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1629996330644397

    APA Style (7th edition)

  • Thaker, Rajsi. Potential drug treatment for Duchenne muscular dystrophy which could be through upregulation of lipin1. 2021. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1629996330644397.

    MLA Style (8th edition)

  • Thaker, Rajsi. "Potential drug treatment for Duchenne muscular dystrophy which could be through upregulation of lipin1." Master's thesis, Wright State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=wright1629996330644397

    Chicago Manual of Style (17th edition)

wright1629996330644397
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This open access ETD is published by Wright State University and OhioLINK.