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Clarification of tau fibrillization pathway in vitro implications to Alzheimer’s disease

Chirita, Carmen Nicoleta
http://rave.ohiolink.edu/etdc/view?acc_num=osu1090942907

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Biophysics.
In vitro tau polymerization in the presence of inducers is a good model for the fibrillization of the protein in Alzheimer’s disease, a process believed to lead to neurodegeneration. Here we characterize the mechanism of tau polymerization induction by free fatty acids and newly identified inducers (anionic surfactants and microspheres and dyes). We show that detergent micelles and phospholipid vesicles nucleate filament formation and this parallels observations from biopsy samples of Alzheimer’s disease patients. We parallel these results with another natively unstructured amyloid forming protein, α-synuclein, and with a homologous microtubule associated protein, MAP2c. Finally, we show that tau polymerization proceeds via a partially folded assembly intermediate and that dye molecules can modulate tau polymerization, by affecting the propensity or the nature of this intermediate. The latter observation has relevance for the therapeutics of Alzheimer’s disease. Drugs that affect tau polymerization in certain ways can be tested for their efficiency and the pathogenicity of the intermediate versus the filament can be assessed.
Jeffrey Kuret (Advisor)
241 p.
Alzheimer's disease, Parkinson's disease; nucleation dependent polymerization, fibrillization, filament formation; tau protein, alpha-synuclein, MAP2c; microtubule associated protein; critical micelle concentration

Recommended Citations

Citations

  • Chirita, C. N. (2004). Clarification of tau fibrillization pathway in vitro implications to Alzheimer’s disease [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1090942907

    APA Style (7th edition)

  • Chirita, Carmen. Clarification of tau fibrillization pathway in vitro implications to Alzheimer’s disease. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1090942907.

    MLA Style (8th edition)

  • Chirita, Carmen. "Clarification of tau fibrillization pathway in vitro implications to Alzheimer’s disease." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1090942907

    Chicago Manual of Style (17th edition)

osu1090942907
1,090
© 2004, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.