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Role of Cofilin, an Actin Cytoskeletal Protein, in Ischemic Conditions: Potential Therapeutic Target for Ischemic Stroke

Madineni, Anusha

Abstract Details

2013, Master of Science in Medicinal Chemistry (MSP), University of Toledo, College of Pharmacy.
Cerebral ischemia or stroke is a condition associated with decreased blood supply to brain leading to death of neurons. It is associated with a diverse cascade of responses involving both degenerative and regenerative mechanisms. Actin cytoskeleton changes play a key role in mediating these responses. Cofilin, an actin cytoskeletal severing protein is known to be involved in early stages of apoptotic cell death. Evidence supports its intervention in progression of disease states like Alzheimer’s and ischemic kidney disease. We have hypothesized possible involvement of cofilin in cerebral ischemia and neurodegeneration. To investigate the potential actin cytoskeletal changes induced by cofilin in ischemia, various ischemic models such as oxidative stress, oxygen glucose deprivation (OGD) in vitro and permanent middle cerebral artery occlusion (pMCAO) in vivo were used. The expression profile studies by immunoblotting and fluorescence methods displayed decrease in phosphocofilin (inactive form of cofilin) levels with all models of ischemia implying stress induced cofilin activation. Furthermore, calcineurin and slingshot 1L (SSH) phosphatases were found to be the signaling mediators of the cofilin activation pathway in ischemia elucidated by our inhibitor studies. These results strongly support cofilin role in cerebral ischemia induced actin cytoskeleton alterations leading to cell damage. We believe targeting this protein mediator has a potential for therapeutic intervention in stroke.
Zahoor Shah, PhD (Committee Chair)
Amanda Bryant-Friedrich, PhD (Committee Member)
Youssef Sari, PhD (Committee Member)
62 p.

Recommended Citations

Citations

  • Madineni, A. (2013). Role of Cofilin, an Actin Cytoskeletal Protein, in Ischemic Conditions: Potential Therapeutic Target for Ischemic Stroke [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1364331841

    APA Style (7th edition)

  • Madineni, Anusha. Role of Cofilin, an Actin Cytoskeletal Protein, in Ischemic Conditions: Potential Therapeutic Target for Ischemic Stroke. 2013. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1364331841.

    MLA Style (8th edition)

  • Madineni, Anusha. "Role of Cofilin, an Actin Cytoskeletal Protein, in Ischemic Conditions: Potential Therapeutic Target for Ischemic Stroke." Master's thesis, University of Toledo, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=mco1364331841

    Chicago Manual of Style (17th edition)