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bioRxiv · 10.64898/2026.03.31.715603

IL-17A rescues motor deficits in a mouse model 1 of Spinocerebellar Ataxia Type 2

Yarden, Y.·Ryu, C.·Huang, C.-T.·song, Y.-H.·Yarom, Y.·Choi, G.
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Abstract

Motor performance and coordination deficits are hallmarks of spinocerebellar ataxias, yet effective disease-modifying therapies remain limited. Here, we investigate the expression of the interleukin 17 receptor subunit A (IL-17RA) in cerebellum and assess the therapeutic potential of its ligand in a mouse model for Spinocerebellar Ataxia Type 2 (SCA2). We found that IL-17RA is highly enriched in cerebellar molecular layer interneurons (MLIs), which provide inhibitory input to Purkinje neurons. In-vitro electrophysiological recordings revealed that symptomatic SCA2 mice exhibited increased spontaneous inhibitory synaptic input onto Purkinje neurons, which was normalized by IL-17A application to control levels. Concomitantly, IL-17A application restored Purkinje neuron firing, a parameter characteristically reduced in SCA2 mice. Behaviorally, intranasal administration of IL-17A restored motor performance of symptomatic SCA2 mice to control levels in both rotarod and beam-crossing assays. Collectively, our results indicate that IL-17A rescues Purkinje neuron dysfunction and motor deficits in SCA2 mice, highlighting IL-17A signaling as a promising therapeutic target for spinocerebellar ataxia.

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Yarden, Y., Ryu, C., Huang, C.-T., song, Y.-H., Yarom, Y., Choi, G.. 2026-04-02. IL-17A rescues motor deficits in a mouse model 1 of Spinocerebellar Ataxia Type 2. https://doi.org/10.64898/2026.03.31.715603

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