2. Academic Validation
  3. PGK1 contributes to blood-brain barrier integrity via PI3K-AKT-mTOR pathway in early pneumococcal meningitis

PGK1 contributes to blood-brain barrier integrity via PI3K-AKT-mTOR pathway in early pneumococcal meningitis

  • Int Immunopharmacol. 2026 Feb 15:171:116163. doi: 10.1016/j.intimp.2026.116163.
Xiao-Hui Liu 1,  Feng Hao 2,  Shu-Xin Zhao 3,  Xiao-Mu Guo 4,  Xiao-Qing Shi 5,  Hui-Wen Geng 6,  Zhuo Zhang 7,  Yong-Juan Xin 3,  Bing Huang 8,  Pei-Pei Liu 9
Affiliations

Affiliations

  • 1 Clinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Kaifeng155 Hospital, China RongTong Medical Healthcare Group Co.Ltd., Kaifeng 475000, Henan, China.
  • 2 Clinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
  • 3 Department of Child and Adolescent Health, Precision Nutrition Innovation Center, School of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
  • 4 Shanxi Medical University, Taiyuan 030000, Shanxi, China.
  • 5 Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Key Laboratory of Laboratory Medicine of Henan Province, Zhengzhou 450052, Henan, China.
  • 6 Clinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
  • 7 Department of Neurology, The First Hospital of Lankao, Kaifeng 475300, Henan, China.
  • 8 Pain and Related Disease Research Laboratory, Shantou University Medical College, Shantou 515000, Guangdong, China; Brain Function and Disease Laboratory, Shantou University Medical College, Shantou 515000, Guangdong, China. Electronic address: [email protected].
  • 9 Clinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: [email protected].
PMID: 41512793 DOI: 10.1016/j.intimp.2026.116163
Abstract

Pneumococcal meningitis continues to be a devastating disease associated with high mortality and neurological sequelae, largely due to disruption of the blood-brain barrier (BBB). Emerging evidence implicates that metabolic reprogramming within the neurovascular unit constitutes a critical pathophysiological mechanism. Phosphoglycerate kinase 1 (PGK1), a glycolytic enzyme, may play a role beyond energy metabolism, but its involvement in BBB protection during meningitis is undefined. Here, we demonstrate that PGK1 preserves BBB integrity via the PI3K-Akt-mTOR pathway in early pneumococcal meningitis. Transcriptomic and in vitro analyses revealed that early Streptococcus pneumoniae Infection induces profound metabolic reprogramming in the BBB microvasculature, characterized by significant upregulation of glycolytic Enzymes including PGK1. Furthermore, PGK1 overexpression in bEnd.3 ells enhanced expression of tight junction proteins (ZO-1, Occludin). Mechanistically, PGK1 conferred barrier protection by fueling ATP production and subsequently activating the PI3K-AKT-mTOR signaling pathway. This conclusion is supported by the finding that inhibition of this pathway abolished the PGK1-dependent upregulation of tight junctions. These findings identify PGK1 as an essential host mediator safeguarding BBB function through the PI3K-AKT-mTOR-tight junction protein axis during early pneumococcal meningitis, highlightingPGK1 and its downstream effectors as novel therapeutic targets to preserve BBB integrity and mitigate neurological damage.

Keywords

Blood−brain barrier; Glycolysis; PGK1; PI3K-AKT-mTOR; Streptococcus pneumoniae meningitis.

Figures
Products