Protein kinase C activity is a protective modifier of Purkinje neuron degeneration in cerebellar ataxia
| العنوان: | Protein kinase C activity is a protective modifier of Purkinje neuron degeneration in cerebellar ataxia |
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| المؤلفون: | Chris I. De Zeeuw, Stefan M. Pulst, Aaron H. Wasserman, Ravi Chopra, Vikram G. Shakkottai |
| المساهمون: | Neurosciences, Netherlands Institute for Neuroscience (NIN) |
| المصدر: | Human Molecular Genetics, 27(8), 1396-1410. Oxford University Press Human Molecular Genetics, 27, 1396-1410. Oxford University Press |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cerebellum, Spinocerebellar Ataxia Type 1, Ataxia, Primary Cell Culture, Mice, Transgenic, Biology, Neuroprotection, Tissue Culture Techniques, Mice, Purkinje Cells, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Journal Article, Animals, Humans, Spinocerebellar Ataxias, Phosphorylation, Molecular Biology, Ataxin-1, Protein Kinase C, Genetics (clinical), Protein kinase C, Ataxin-2, Cerebellar ataxia, Neurodegeneration, Articles, Microtomy, General Medicine, medicine.disease, Cell biology, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, nervous system, medicine.symptom, 030217 neurology & neurosurgery, Signal Transduction |
| الوصف: | Among the many types of neurons expressing protein kinase C (PKC) enzymes, cerebellar Purkinje neurons are particularly reliant on appropriate PKC activity for maintaining homeostasis. The importance of PKC enzymes in Purkinje neuron health is apparent as mutations in PRKCG (encoding PKCγ) cause cerebellar ataxia. PRKCG has also been identified as an important node in ataxia gene networks more broadly, but the functional role of PKC in other forms of ataxia remains unexplored, and the mechanisms by which PKC isozymes regulate Purkinje neuron health are not well understood. Here, we investigated how PKC activity influences neurodegeneration in inherited ataxia. Using mouse models of spinocerebellar ataxia type 1 (SCA1) and 2 (SCA2) we identify an increase in PKC-mediated substrate phosphorylation in two different forms of inherited cerebellar ataxia. Normalizing PKC 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 PKC targets limits Purkinje neuron membrane excitability, suggesting that PKC activity may support Purkinje neuron health by moderating excitability. These data suggest a functional role for PKC enzymes in ataxia gene networks, and demonstrate that increased PKC activity is a protective modifier of degeneration in inherited cerebellar ataxia. |
| اللغة: | English |
| تدمد: | 0964-6906 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c70593bbe75e8d0cf13b439a5d364ec https://hdl.handle.net/20.500.11755/801680bb-bd23-472a-b343-b6c8343f7d67 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8c70593bbe75e8d0cf13b439a5d364ec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09646906 |
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