Seyeon Kim. (2025). Investigating the role of PTP1B in neurodegenerative mechanisms induced by ALS/FTD-associated RNA-binding proteins. doi: 10.22677/THESIS.200000837594
Type
Thesis
Description
Neurodegenerative diseases, RBP, Neuroinflammation, Protein quality contorl, PTP1B
Table Of Contents
Chapter Ⅰ. Introduction 1 1.1 Research background and purpose 1 1.2 Neurodegenerative disease (ALS and FTD) 1 1.3 RNA binding protein associated with ALS and FTD 4 1.4 Neuroinflammation 8 1.5 Cellular processes of protein quality control system 8
Chapter Ⅲ. Results 21 Part 1. Non-cell autonomous effects of astrocytes in contributing to neuronal cell death 21 Part 1-1. The role of PTP1B inhibition in alleviating neuroinflammation associated with TDP-43 22 3.1 Investigating the role of PTP1B in CNS 22 3.2 PTP1B is an essential modulator of TDP-43-induced inflammation in astrocytes 24 3.3 PTP1B regulates TDP-43-induced inflammation via the NF-κB pathway 32 3.4 PTP1B inhibition and absorption of proinflammatory cytokines mitigate the neuronal toxicity caused by astrocytic TDP-43 overexpression 37 3.5 PTP1B inhibition suppresses astrocytic TDP-43-induced mitochondrial dysfunction and spine retraction in neurons 45 3.6 PTP1B inhibition ameliorates astrocytic TDP-43-induced neuronal toxicity and mitochondrial dysfunction in motor neuron-like cells 50 3.7 Inflammation and neuronal toxicity induced by glial TDP-43 are mitigated by PTP1B downregulation in Drosophila 55 Part 1-2. The effects of DHE in mitigating neuroinflammation related to mutant FUS in astrocytes 65 3.8 Investigating the role of natural compound-derived PTP1B inhibitors in CNS 65 3.9 DHE alleviates aggregation of FUS P525L and activation of inflammatory response in mutant FUS P525L overexpressed astrocytes 66 3.10 DHE treatment reduces astrocytic FUS P525L-induced neuronal toxicity and mitochondria dysfunction 73 3.11 DHE treatment rescues glial FUS induced toxicity in Drosophila 76 3.12 DHE treatment moderates inflammatory response in FUSALS patient fibroblast 83 Part 2. Cell-autonomous effects of TDP-43 on UPS impairment 88 3.13 The mitigating effects of PTP1B inhibition on UPS impairment dysregulation in neuronal cells 89 3.14 Induced ALP by TDP-43 overexpression is restored though inhibition of PTP1B in N2a 96 3.15 Inhibition of PTP1B ameliorates TDP-43-induced neurotoxicity in vitro and in vivo 101 3.16 PTP1B overexpression exacerbates TDP-43-induced neurotoxicity 106
Chapter Ⅳ. Discussion 113 References 120 Abstracts in Koreans 133
