https://scholar.dgist.ac.kr/handle/20.500.11750/283 2026-08-03T10:44:05Z 2026-08-03T10:44:05Z 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 https://scholar.dgist.ac.kr/handle/20.500.11750/60547 2026-07-30T10:40:13Z 2026-05-31T15:00:00Z

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 Hong, Jihyun An, Hyun-Kyu Nam, Hyeri Choi, Jieun Yu, Seong-Woon https://scholar.dgist.ac.kr/handle/20.500.11750/59942 2026-02-05T11:10:17Z 2025-11-30T15:00:00Z

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 Kim, Dayoung Lee, Younghwan Kim, Sangjae Yu, Seong-Woon https://scholar.dgist.ac.kr/handle/20.500.11750/58961 2025-08-29T02:10:11Z 2025-09-30T15:00:00Z

Title: Anti-depressant effects of a human telomerase-derived peptide GV1001 in an animal model of chronic restraint stress Author(s): Kim, Dayoung; Lee, Younghwan; Kim, Sangjae; Yu, Seong-Woon Abstract: Depression is a common cause of mental illness in the modern world, and the wide variation in symptoms makes it difficult to develop suitable antidepressants. The commonly used serotonin reuptake inhibitors (SSRIs) cause many side effects, making it imperative to develop alternative treatments. GV1001, a 16-amino acid peptide derived from human telomerase reverse transcriptase, has shown various neuroprotective effects in recent studies. However, its effects on depression were unknown. In this study, we found that the administration of GV1001 rescued cognitive deficits, anxiety-, and depressive-like behaviors in a mouse model of chronic restraint stress (CRS). GV1001 efficiently reduced the increased serum corticosterone level and suppressed activation of the hypothalamic CRH neurons, suggesting the modulation of the hypothalamus-pituitary-adrenal axis. Collectively, our findings provide evidence for a novel antidepressant efficacy of GV1001.

2025-09-30T15:00:00Z Jeong, Hyeonjeong Choe, Seongwon Jung, Seonghee Yu, Seong-Woon https://scholar.dgist.ac.kr/handle/20.500.11750/58255 2025-07-25T03:34:30Z 2025-02-28T15:00:00Z

Title: Neural stem cell-specific deletion of Atg7 alleviates hippocampal dysfunction and neuronal alterations induced by chronic restraint stress Author(s): Jeong, Hyeonjeong; Choe, Seongwon; Jung, Seonghee; Yu, Seong-Woon Abstract: Adult hippocampal neurogenesis is inhibited by chronic psychological stress and impaired neurogenesis underlies stress-related psychological disorders. We previously reported that chronic restraint stress (CRS) evokes autophagic death of adult hippocampal neural stem cells (NSCs) while NSC-specific deletion of Atg7 prevents death of NSCs. Examination of cognitive ability and mood regulation next day of the termination of stress showed normal hippocampal function in mice deficient of Atg7. However, it was not investigated whether the preservation of NSC pool alleviates hippocampal neuronal alterations. Here, we show that CRS increased c-Fos-positive, activated neurons in the granule cell layer and decreased spine density of CA3 neurons in the hippocampus, and these hippocampal neuronal deficits were prevented by NSC-specific deletion of Atg7. Of note, our observation was conducted right after the termination of CRS. Therefore, our results suggest that the detrimental effects of stress on hippocampal neurons can be buffered by NSCs independent of neurogenesis and NSCs are essential to the hippocampal function both through the neurogenesis-dependent developmental process and by direct regulation of neural activation.

2025-02-28T15:00:00Z