A miR-383-5p Signaling Hub Coordinates the Axon Regeneration Response to Inflammation

• DOI: 10.1523/jneurosci.1822-23.2024
• Publication Date: 2024-09-12T17:50:25Z
• Authors: Matthew A. Hinter...; Camille A. Juźwik; Barbara Morquette; Elizabeth Hua; Julia Zhang; Sienna Drake; Shan Shan Shi; Isabel Rambaldi; Vamshi Vangoor; Jeroen Pasterkamp; Craig Moore; Alyson E. Fournier
• Keywords: Ciliary neurotrophic factor

Neuroinflammation can positively influence axon regeneration following injury in the central nervous system (CNS). Inflammation promotes release of neurotrophic molecules and stimulates intrinsic pro-regenerative molecular machinery neurons, but detailed mechanisms driving this effect are not fully understood. We evaluated how microRNAs regulated retinal neurons response to intraocular inflammation identify their potential role regeneration. found that miR-383-5p is downregulated ganglion cells zymosan-induced inflammation. MiR-383-5p downregulation sufficient promote growth vitro , intravitreal injection a inhibitor into eye optic nerve crush. directly targets ciliary factor (CNTF) receptor components inhibition sensitizes adult outgrowth-promoting effects CNTF. Interestingly, we also demonstrate CNTF treatment reduce levels constituting positive-feedback module whereby initial reduces levels, which then disinhibits sensitize ligand. Additionally, de-represses mitochondrial antioxidant protein peroxiredoxin-3 (PRDX3) was required for associated with loss function vitro. have thus identified positive feedback mechanism facilitates neuronal sensitivity new signalling inflammation-induced Significance statement both negatively injury. Identifying pathways mimic while bypassing cytotoxic important our understanding precise functions CNS repair. suppressed inflammatory stimuli regulates members complex, as well expression an improve crush model. These findings may bypass detrimental