Description
- Abstract:
- Population over the age of 65 is at a high risk of neurodegenerative diseases, especially Alzhiemer’s disease (AD), but there are currently no effective therapeutics to treat AD. Adult Hippocampal Neurogenesis (AHN), a process in which Neural Stem Cells (NSCs) proliferate and differentiate into newborn neurons, is significantly decreased in AD patients. Bone Morphogenic Protein (BMP) signaling increases in these patients and inhibits AHN. Although blocking the BMP signaling pathway to increase AHN seems appealing, it is not ideal to completely abolish BMP because BMP is involved in several other pathways. One possible drug target for increasing AHN is the Muscle Specific Kinase (MuSK) protein. MuSK Immunoglobulin 3 domain interacts with BMP and enhances BMP signaling pathway to transcribe AHN-suppressing genes. The Fallon Lab aims to induce alternative splicing with antisense oligonucleotides (ASO) and skip MuSK Ig3 domain to improve AHN in AD patients. While the Fallon Lab successfully designed lead candidate ASOs and assessed their efficiency in myoblasts, we have limited knowledge on MuSK expression on our cell of interest, NSCs. To examine whether our ASOs have a valid target in NSCs, I profiled MuSK at the transcript and protein levels in NSCs. Previous studies in the Fallon Lab discovered the MuSK transcript variant T2 in the hippocampus, which lacks Ig1 and Ig2 domains. In this study, I extended this variant study and demonstrated that T2 transcript spans the Ig3 domain to tyrosine kinase domain. I also observed that T2 is the predominant transcript of MuSK in the hippocampus, but not in the rest of the brain or in NSCs. Using immunocytochemistry, I also found that MuSK protein encoded by the T1 transcript is expressed in NSCs, indicating that NSCs will be targeted by our ASOs and may induce AHN. Our future work will focus on assessing the effect of ASOs on the proliferation of NSCs.
- Notes:
- Thesis (Sc. M.)--Brown University, 2024
Citation
Choi, Sei Hyun,
"Characterization of MuSK Transcripts and Proteins in Neural Stem Cells"
(2024).
Biology and Medicine Theses and Dissertations, Biotechnology.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:q4dga2xa/
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