2. Academic Validation
  3. GNE-317 ameliorates neuroinflammation stimulated by lipopolysaccharide via PI3K/Akt/mTOR pathway

GNE-317 ameliorates neuroinflammation stimulated by lipopolysaccharide via PI3K/Akt/mTOR pathway

  • Pharmacol Rep. 2026 Apr;78(2):505-518. doi: 10.1007/s43440-026-00832-y.
Yoojin Lee 1,  Namkwon Kim 2,  Haeun Hwang 1,  Subyn Jeon 1,  Seung Ho Jeon 1,  Yeongae Lee 1,  Jeongmin Son 1,  Sumin Ma 1,  Sora Yoon 1,  Min Sung Gee 3,  Kyoung-Lim Kim 4,  Kyung-Soo Inn 1 2 4 5,  Inwha Baek 6 7 8,  Jong Kil Lee 9 10
Affiliations

Affiliations

  • 1 Department of Fundamental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
  • 2 Department of Pharmacy, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
  • 3 Department of Neurobiology and Behavior, University of California, 3208 Biological Sciences III, Irvine, CA, 02447, USA.
  • 4 Department of Regulatory Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
  • 5 Institute of Regulatory Innovation through Science (IRIS), Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
  • 6 Department of Pharmacy, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. [email protected].
  • 7 Department of Regulatory Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. [email protected].
  • 8 Institute of Regulatory Innovation through Science (IRIS), Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. [email protected].
  • 9 Department of Fundamental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. [email protected].
  • 10 Department of Pharmacy, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. [email protected].
PMID: 41634514 DOI: 10.1007/s43440-026-00832-y
Abstract

BACKGROUND: Microglial activation in the central nervous system plays a central role in neuroinflammation and contributes to the onset and progression of neurodegenerative diseases. This study aimed to evaluate the anti-inflammatory effects of GNE-317, a phosphoinositide 3-kinase/ mammalian target of rapamycin (PI3K/mTOR) inhibitor, in lipopolysaccharide (LPS)-induced neuroinflammatory models. METHODS: BV2 microglial cells were stimulated with LPS, and the effects of GNE-317 were examined using Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), nitric oxide (NO) assays, and immunofluorescence. For in vivo experiments, C57BL/6 mice received GNE-317 (25 mg/kg/day, intraperitoneal, IP) for three days, followed by LPS injection (5 mg/kg, IP). Microglial activation was assessed by anti-ionized calcium-binding adapter molecule-1 (IBA1) immunostaining in the brain. RESULTS: GNE-317 inhibited PI3K/protein kinase B (Akt)/mTOR signaling and reduced nuclear factor-kappa B (NF-κB) nuclear translocation in LPS-stimulated BV2 cells. It decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression and lowered tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production. In LPS-injected mice, GNE-317 reduced microglial activation in brain tissue. CONCLUSIONS: GNE-317 attenuates neuroinflammation by suppressing microglial activation through inhibition of the PI3K/Akt/mTOR and NF-κB pathways, supporting its potential as a therapeutic agent for microglia-mediated neuroinflammatory diseases.

Keywords

GNE-317; Lipopolysaccharide; Neurodegenerative diseases; Neuroinflammation; Nuclear factor κB.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12763
    98.76%, PI3K/mTOR Inhibitor