https://scholar.dgist.ac.kr/handle/20.500.11750/281 2026-11-05T04:49:37Z https://scholar.dgist.ac.kr/handle/20.500.11750/61083 Title: Microglial protein kinase CK2 prevents obesity in mice potentially through NLRP3 inflammasome activation Author(s): Lee, Ji-Won; Kim, Nayoun; Kim, Seolsong; Park, Seokjae; Nam, Hyeri; Lee, Younghwan; Hwang, Seohyeon; Lee, Yeim; Ha, Sehee; Koo, Wonkeon; Kim, Eun-Kyoung; Yu, Seong-Woon Abstract: Protein kinase CK2 plays an important role in the regulation of metabolism and obesity. However, the metabolic role of CK2 and its substrates in the brain remain largely unknown. Here, we show that microglial CK2 is required for metabolic homeostasis through ASC phosphorylation and subsequent NLRP3 inflammasome-mediated interleukin (IL)-18 maturation and release. Mice with microglia-specific, inducible deletion of CK2 regulatory subunit beta (CK2 beta) showed obese phenotypes with weight gain, abnormal glucose homeostasis, and decreased energy expenditure. At the molecular level, CK2 phosphorylated ASC at T154, and this phosphorylation was essential for ASC aggregation and NLRP3 inflammasome activation. Microglial deletion of CK2 beta decreased central production of IL-18, mirroring the obese phenotypes of mice lacking IL-18 signaling. Our results suggest that the microglial CK2-ASC-NLRP3 axis underlies the central regulation of metabolic homeostasis and prevents obesity through processing and secretion of IL-18. Nevertheless, a gap remains between these molecular mechanistic findings and the observed in vivo behavioral and metabolic phenotypes, highlighting the need for future systems-level analyses to fully delineate the broader substrate landscape of CK2 and to integrate the functional outcomes of CK2 deficiency in microglia with in vivo phenotypes. 2026-08-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60547 Title: A human telomerase reverse transcriptase-derived peptide GV1001 rescues neurodegeneration in a mouse model of Alzheimer disease Author(s): Lee, Younghwan; Nam, Hyeri; Lee, Ji-Won; Ko, Yeo Jin; Kim, Eum Ji; Ha, Sehee; Kim, Nan; Koo, Ja Wook; Son, Taekwon; Kim, Sangjae; Yu, Seong-Woon Abstract: GV1001 is a peptide consisting of 16 amino acids derived from the catalytic subunit of human telomerase reverse transcriptase. A recent phase II clinical trial in patients with Alzheimer disease (AD) showed that GV1001 effectively improved memory impairment with proven safety, leading to larger clinical trials. However, the mechanisms underlying therapeutic effects of GV1001 on AD remain elusive. Here, we report that GV1001 reduces amyloid plaque burden and rescues synaptic loss and memory deficits in 5xFAD mice by increasing microglial migration toward large amyloid plaques and amyloid beta degradation. Single-cell RNA-sequencing revealed that GV1001 promoted the migratory and phagocytic phenotypes by modulating disease-associated microglial profiles. At the molecular level, through virtual target screening and docking simulation combined with peptide pulldown, we identified that bradykinin receptor 1 is the binding target of GV1001. Furthermore, we revealed that GV1001 facilitated microglial migration and amyloid beta phagocytosis in an mTORC2-dependent manner. Collectively, our work demonstrates the amyloidolytic effects and the relevant in-depth signaling mechanism of GV1001 in microglia, suggesting GV1001 as a promising disease-modifying therapeutic agent for AD. 2026-05-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60241 Title: RITA 또는 이의 유도체를 포함하는 뇌신경계 질환 예방 또는 치료용 조성물 Author(s): 정성희; 유성운 https://scholar.dgist.ac.kr/handle/20.500.11750/59942 Title: Presenilin 2 regulates corticosterone-induced autophagic death of adult hippocampal neural stem cells Author(s): Hong, Jihyun; An, Hyun-Kyu; Nam, Hyeri; Choi, Jieun; Yu, Seong-Woon Abstract: Chronic psychological stress is a well-known risk factor for neurodegenerative diseases including Alzheimer disease (AD), yet the underlying mechanisms remain unclear. We previously showed that chronic stress impairs adult hippocampal neurogenesis by triggering autophagic cell death of adult hippocampal neural stem (HCN) cells. Impairment of adult hippocampal neurogenesis is widely observed in the brains of human AD patients and animal models. However, it remains unknown whether stress-induced death of HCN cells is related to the pathogenesis of AD. In this study, we investigated whether the stress hormone, corticosterone (CORT) induces HCN cell death through presenilin 2 (Psen2), a gene associated with familial AD. Using CRISPR/Cas9-based knockout models and in vitro CORT treatment, we found that Psen2 expression is upregulated by CORT and Psen2 deletion prevents CORT-induced death in HCN cells. However, the Psen2 N141I mutation, despite its pathogenicity in AD, did not exacerbate CORT-induced cell death in vitro and hippocampus-dependent behavioral deficits in vivo. These findings indicate that while Psen2 is essential for stress-induced death of HCN cells, the Psen2 N141I mutation alone may not be sufficient to link chronic stress to AD pathogenesis. 2025-11-30T15:00:00Z