Date of Graduation

12-2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Cell & Molecular Biology (PhD)

Degree Level

Graduate

Department

Cell & Molecular Biology

Advisor/Mentor

Thallapuranam, Suresh

Committee Member

Adams, Paul D.

Second Committee Member

Fan, Chenguang

Third Committee Member

Hettiarachchy, Navam S.

Keywords

Protein aggregation; Protein folding; Heparin

Abstract

Nature achieves molecular self-assembly through the ordered growth of nanoscale building blocks with high efficiency to fabricate macromolecular architectures. One example of self- assembly is peptides folding onto protein is one of the most astounding biological self-assembly processes. When proteins aggregate to form amyloid fibers, the secondary structure of the protein converts from its native state to a cross-beta-sheet. Fibroblast growth factors (FGFs) possess an essential role in neuronal survival during development. In addition, they are involved in neural stem cell (NSC) proliferation. Fibroblast growth factors (FGFs) are well known to be synthesized in the central nervous system (CNS) and act on (CNS) cells in vitro. High levels of acidic fibroblast factor (aFGF) expression were observed in motoneurons, primary sensory neurons, and retinal ganglion neurons. It has been indicated that the neurogenesis process is controlled by fibroblast growth factor receptors 1, 2, and 3, and the co-activation of fibroblast growth factors 1 and 3 affect the symmetrical divisions of (NSC). Therefore, the inactivation of either one of them will cause asymmetrical divisions and neurogenesis. Fibroblast growth factor-1 (FGF-1) is the universal ligand of fibroblast growth factors because it strongly binds to all four fibroblast growth factors receptors (FGFR1- 4) to trigger a range of actions, wound healing, and neurogenesis. We carried out this study to determine the factors that lead to (FGF-1) aggregation in the cell membrane. Various neurodegenerative disorders have been correlated with (FGF-1). For example, the elevation of FGF-1 in Alzheimer's disease. Also, (FGF-1) reduces the accumulation of α-synuclein and its neurotoxicity that causes Parkinson’s disease (PD). Hence, our study might be a step toward understanding one of the most important causes of these neurodegenerative disorders and might assist in finding a cure for them.

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