Researcher ORCID Identifier
0009-0005-2197-698X
Graduation Year
2025
Date of Submission
12-2024
Document Type
Open Access Senior Thesis
Degree Name
Bachelor of Arts
Department
Neuroscience
Reader 1
Sandra Watson, PhD
Reader 2
Daniel Mordes, PhD
Terms of Use & License Information
Rights Information
© 2024 Vikram Chatterjee
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease characterized by motor neuron loss and the pathological accumulation of misfolded proteins. Autophagy, a lysosome-mediated clearance mechanism, plays a vital role in maintaining cellular homeostasis by removing damaged organelles and protein aggregates. Impairments in autophagy have been increasingly linked to ALS, underscoring its importance in neuronal health. TANK-binding kinase 1 (TBK1) is a key regulator of selective autophagy, facilitating the recognition and sequestration of specific cargo through phosphorylation of autophagy receptors. Notably, mutations in the TBK1 gene have been identified in ALS patients, directly implicating TBK1 dysfunction in disease pathogenesis. Through previous phosphoproteomic studies, nuclear receptor coactivator 7 (NCOA7) was identified as a potential TBK1 substrate. It was hypothesized to function as a selective autophagy receptor, given its involvement in lysosomal activity and its genetic similarity to nuclear receptor coactivator 4 (NCOA4), a known autophagy receptor. Using induced pluripotent stem cells (iPSCs), gene editing, proteomic analysis, and fluorescence-based analyses, this study examines NCOA7’s relationship with TBK1 and its potential role in regulating neuronal autophagy. Results suggest that TBK1 plays a role in maintaining lysosomal function and autophagic processes under certain conditions, though its precise contribution to lysosomal acidification and autophagosome maturation requires further validation. However, evidence supporting NCOA7’s role as a selective autophagy receptor was inconclusive under cellular stress conditions. Future studies should focus on refining experimental models, such as iPSC-derived neurons. Additionally, utilizing advanced proteomic and lysosome-imaging techniques can further elucidate the roles of TBK1 and NCOA7 in autophagy and their contributions to ALS pathogenesis.
Recommended Citation
Chatterjee, Vikram, "Regulation of Neuronal Autophagy by Amyotrophic Lateral Sclerosis (ALS) - Associated Kinase TBK1: Evaluating the Role of NCOA7" (2025). CMC Senior Theses. 3872.
https://scholarship.claremont.edu/cmc_theses/3872
