Protein kinase C activity is a protective modifier of Purkinje neuron degeneration in cerebellar ataxia.

Among the many types of neurons expressing protein kinase C enzymes, cerebellar Purkinje neurons are particularly reliant on appropriate activity for maintaining homeostasis. The importance of duanyu1531 enzymes in Purkinje neuron health is apparent as mutations in PRKCG (encoding cause cerebellar ataxia. PRKCG has also been identified as an important node in ataxia gene networks more broadly, but the functional role of duanyu1531 in other forms of ataxia remains unexplored, and the mechanisms by which duanyu1531 isozymes regulate Purkinje neuron health are not well understood. Here, we investigated how duanyu1531 activity influences neurodegeneration in inherited ataxia. Using mouse models of spinocerebellar ataxia type 1 (SCA1) and 2 (SCA2) we identify an increase in substrate phosphorylation in two different forms of inherited cerebellar ataxia. Normalizing duanyu1531 substrate phosphorylation in SCA1 and SCA2 mice accelerates degeneration, suggesting that the increased activity observed in these models is neuroprotective. We also find that increased phosphorylation of duanyu1531 targets limits Purkinje neuron membrane excitability, suggesting that duanyu1531 activity may support Purkinje neuron health by moderating excitability. These data suggest a functional role for duanyu1531 enzymes in ataxia gene networks, and demonstrate that increased duanyu1531 activity is a protective modifier of degeneration in inherited cerebellar ataxia.

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