Curcumin Promotes Myelin Repair after Spinal Cord Injury via Spatially Selective Regulation of CLASP2 Phosphorylation

作者：Ruifan Lin, Wenya Gao, Xianming Wu, Ninan Zhang, HongLin Xu, Chunnuan Lin, Xiahe Huang, Yingchun Wang, Wenxiang Meng, Qi Xie · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2026 · DOI：10.64898/2026.01.21.700776 · 研究领域：Neurogenesis and neuroplasticity mechanisms、Nerve injury and regeneration、Curcumin's Biomedical Applications

Abstract Spinal cord injury (SCI) remains a devastating neurological disorder, where limited axonal regeneration and inefficient remyelination severely restrict recovery. Although curcumin has recognized neuroprotective properties, its mechanism in myelin repair is unclear. Here, we identify a phosphorylation-dependent cytoskeletal pathway as a key target of curcumin. In a mouse spinal cord transection model, curcumin treatment improved hindlimb motor function, reduced fibrotic scarring, and increased myelin basic protein (MBP) in the injured region. Phosphoproteomic profiling revealed cytoskeletal regulation as a major process affected by curcumin, with CLASP2 emerging as a critical target. Curcumin enhanced CLASP2 phosphorylation at Ser1025, a modification that strengthened Golgi association and increased EB1 distribution at the cell periphery, thereby promoting microtubule anchoring without altering global stability. This spatially selective regulation provides a novel mechanism by which curcumin fine-tunes cytoskeletal organization to support remyelination. Analysis of published single-cell sequencing data further showed CLASP2 enrichment in myelin-forming cells, underscoring its relevance. Unlike prior studies emphasizing anti-inflammatory or antioxidant effects, our findings reveal a defined molecular mechanism linking curcumin to cytoskeletal remodeling and myelin repair, highlighting its potential as a safe and accessible therapeutic candidate for SCI.