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

Lin, R.; Gao, W.; Wu, X.; Zhang, N.; Xu, H.; Lin, C.; Huang, X.; Wang, Y.; Meng, W.; Xie, Q.

doi:10.64898/2026.01.21.700776

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bioRxiv · 10.64898/2026.01.21.700776

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

Lin, R.·Gao, W.·Wu, X.·Zhang, N.·Xu, H.·Lin, C.·Huang, X.·Wang, Y.·Meng, W.·Xie, Q.

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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.

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Lin, R., Gao, W., Wu, X., Zhang, N., Xu, H., Lin, C., Huang, X., Wang, Y., Meng, W., Xie, Q.. 2026-01-21. Curcumin Promotes Myelin Repair after Spinal Cord Injury via Spatially Selective Regulation of CLASP2 Phosphorylation. https://doi.org/10.64898/2026.01.21.700776

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