Galectin- related protein, a key contributor, drives diabetes- associated neuropathic pain

• 成果类型: Article
• 署名作者: Chen, Danyang; Wang, Jing; Song, Xiang - Jie; Ding, Zi - Jiao; Lou, Qianqian; Chen, Yuan - Yuan; Wang, Meng - Yuan; Yang, Xin - Lu; Zhang, Zhi; Li, Juan; Wang, Wei; Wang, Haitao
• 署名单位: Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Anhui Medical University; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Anhui Medical University; Anhui Medical University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2527641122
• 发表日期: 2025-12-16
• 页码: e2527641122
• 关键词: diabetes-associated neuropathic pain; galectin-related protein; anterior cingulate cortex; d-serine; astrocytes; neurons

摘要

Neuropathic pain associated with central sensitization is common in diabetic patients, but the underlying mechanisms remain unclear. Here, a proteomics screen identified a previously uncharacterized protein, galectin-related protein (LGALSL), which was significantly upregulated in cerebrospinal fluid and extracellular fluid of the anterior cingulate cortex (ACC) in diabetes-related neuropathic pain (DNP) model rats. Exogenous LGALSL administration reduced mechanical nociceptive thresholds by activating glutamatergic neurons in the ACC (ACCGlu).Chemogenetic manipulations and functional assays revealed that neuron-derived LGALSL directly binds to vimentin on ACC astrocytes, activating those astrocytes. These activated astrocytes subsequently maintain ACCGlu hypersensitivity, driving mechanical hypersensitivity in diabetic rats. Blocking LGALSL-vimentin interactions with a synthetic peptide alleviated LGALSL-induced mechanical hypersensitivity.This study establishes LGALSL-dependent astrocyte-mediated hyperactivation ofACCGlu neurons as a new pathological mechanism of neuropathic pain in diabetes.