Abstract
Neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease are linked to mitochondrial dysfunction and the underexpression of TOM40, a protein with chaperone-like qualities that is responsible for transporting precursor proteins into the mitochondria. Overexpression of TOM40 is reported to partially restore mitochondrial dysfunction and decrease the accumulation of neurotoxic aggregates of α-synuclein. Our goal is to develop an effective method for delivery of TOM40 protein to the brain.
Previous studies have used lentiviruses to carry TOM40 into the hippocampus of α-synuclein transgenic mice. The disadvantage of lentiviral transfection is the random insertions of the target gene into the host genome, which could cause toxic effects. Synthetic phospholipid vesicles containing TOM40 were considered as an alternative delivery method, but these "liposomes" elicit not only toxicity, but also an immune response. Thus, development of a safer delivery method of TOM40 protein is needed. We investigated exosomes, which are extracellular vesicles originating from multivesicular endosomes filled with protein, lipid, or RNA cargoes for cell-cell communication. Since exosomes are created from host cells, they are non-immunogenic and may be a more desirable method.
Expression constructs have been made for the production of TOM40 protein within or on the surface of exosomes. In order to target the delivery of TOM40 to the brain, we attached peptides to the surface of the exosomes, which specifically interact with receptors on neural cells. We attempted to confirm the functionality of the expression constructs through immunocytochemistry followed by flow cytometry and Western blotting.
Thesis Completion
2018
Semester
Spring
Thesis Chair/Advisor
Sugaya, Kiminobu
Degree
Bachelor of Science (B.S.)
College
College of Medicine
Department
Burnett School of Biomedical Sciences
Degree Program
Biomedical Sciences
Location
College of Medicine
Language
English
Access Status
Open Access
Length of Campus-only Access
5 years
Release Date
5-1-2023
Recommended Citation
Holman, Heather, "Targeted Delivery of a Therapeutic Protein for the Treatment of Alzheimer's Disease" (2018). Honors Undergraduate Theses. 328.
https://stars.library.ucf.edu/honorstheses/328