Title

Leveraging high-resolution mass spectrometry- based quantitative proteomics for drug discovery in peripheral nerve degeneration

DGIST Authors

Nguyen Ngoc Chau Thy ; Min-Sik Kim ; Yun-Il Lee

Advisor

김민식

Co-Advisor(s)

Yun-Il Lee

Issued Date

2026

Awarded Date

2026-08-01

Type

Thesis

Description

LC-MS/MS, quantitative proteomics, phospho-proteomics, Schwann cell, peripheral nerve degeneration, drug discovery

Table Of Contents

I. INTRODUCTION 1
1.1 Peripheral neuropathy 1
1.2 Schwann cell’s role in Wallerian degeneration 2
1.3 Liquid chromatography - mass spectrometry （LC-MS） based proteomics in biomedical research 4
II. TEMPORAL PROTEOMICS PROFILING OF PERIPHERAL NERVE DEGENERATION 8
2.1 Introduction 8
2.2 Material and Methods 9
2.2.1 LC-MS/MS sample preparation 9
2.2.2 LC-MS/MS data acquisition 10
2.3 Results 11
2.3.1 Assessment of proteomic methodology and data quality 11
2.3.2 Quantitative temporal proteomics captures the time-dependent profile of degeneration 12
2.3.3 Functional enrichment reveals dynamic protein regulations 12
III. SYNTHETIC BENZODIAZEPINE’S DERIVATIVE MITIGATES PERIPHERAL NERVE DEGENERATION VIA STALLING SCHWANN CELL’S CELL CYCLE PROGRESSION 19
3.1 Introduction 19
3.2 Materials and Methods 20
3.2.1 LC-MS/MS sample preparation 20
3.2.2 LC-MS/MS data acquisition 21
3.2.3 Global proteomics data analysis 22
3.2.4 Phospho-proteomics data analysis 22
3.3 Results 23
3.3.1 Compound 3a suppressed expression cell cycle regulator Cdk1 in Schwann cells 23
3.3.2 Compound 3a interfered with cell cycle’s kinase activity 24
3.3.3 In silico target prediction reveals 3a-Cdk1 interaction 25
3.4 Discussion 25
IV. INHIBITING MST1/2 ALTERS PROTEOMIC SIGNATURES OF DE-DIFFERENTIATED SCHWANN CELLS 32
4.1 Introduction 32
4.2 Material and Methods 35
4.2.1 Global peptide preparation 35
4.2.2 LC-MS/MS data acquisition 36
4.2.3 Database searching and data analysis 36
4.2.4 Gene Ontology analysis 37
4.3 Results 38
4.3.1 XMU inhibits Hippo signalling in de-differentiated Schwann cells 38
4.3.2 XMU restores the cellular processes of Schwann cells 38
4.3.3 XMU and 3a treatments regulate convergent signaling pathways against de-differentiation and proliferation of Schwann cells 39
4.4 Discussion 44
V. CONCLUSION 47
REFERENCES 49

URI

https://scholar.dgist.ac.kr/handle/20.500.11750/60729
http://dgist.dcollection.net/common/orgView/200001014505

DOI

10.22677/THESIS.200001014505

Degree

Doctor

Department

Department of New Biology

Publisher

DGIST

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