Restoring neuronal iron homeostasis revitalizes neurogenesis after spinal cord injury
Huimin Geng # 1 2, Zhiwei Li # 2 3, Zheng Li 2 3, Yuqi Zhang 2, Zhiliang Gao 1, Lei Sun 4, Xingang Li 2, Jiwei Cui 1, Shilei Ni 2 3, Jingcheng Hao 1
Proc Natl Acad Sci U S A. 2023 Nov 14;120(46):e2220300120. doi: 10.1073/pnas.2220300120. Epub 2023 Nov 10.
PMID: 37948584 DOI: 10.1073/pnas.2220300120
Abstract
Spinal cord injury (SCI) can lead to iron overloading and subsequent neuronal ferroptosis, which hinders the recovery of locomotor function. However, it is still unclear whether the maintenance of neuronal iron homeostasis enables to revitalize intrinsic
neurogenesis. Herein, we report the regulation of cellular iron homeostasis after SCI via the chelation of excess iron ions and modulation of the iron transportation pathway using polyphenol-based hydrogels for the revitalization of intrinsic
neurogenesis. The reversed iron overloading can promote neural stem/progenitor cell differentiation into neurons and elicit the regenerative potential of newborn neurons, which is accompanied by improved axon reinnervation and remyelination. Notably,
polyphenol-based hydrogels significantly increase the neurological motor scores from ~8 to 18 (out of 21) and restore the transmission of sensory and motor electrophysiological signals after SCI. Maintenance of iron homeostasis at the site of SCI using
polyphenol-based hydrogels provides a promising paradigm to revitalize neurogenesis for the treatment of iron accumulation-related nervous system diseases.

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