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  • Title: Inositol 1,4,5-trisphosphate receptors and protein kinase C in olivopontocerebellar atrophy.
    Author: Desaiah D, Vig PJ, Subramony SH, Currier RD.
    Journal: Brain Res; 1991 Jun 21; 552(1):36-40. PubMed ID: 1655168.
    Abstract:
    We examined protein kinase C (PKC) activity and inositol 1,4,5-trisphosphate (InsP3) binding in frontal cortex (FC) and cerebellar cortex (CC) of normal humans, patients with dominant ataxia ("C" kindred) and in Lurcher mutant mouse brain (LMB), a suggested animal model for olivopontocerebellar atrophy (OPCA). PKC activity and [3H]InsP3 binding were decreased in CC of human OPCA by 70% and 90% respectively. The decreases were specific to CC as there were no changes in FC. PKC activity and [3H]InsP3 binding in cerebellum (CB) of LMB were similarly decreased as compared to normal littermate controls. The LMB decrease of PKC and [3H]InsP3 binding was evident on the 15th day of age, the day of onset of ataxia. InsP3-mediated calcium release was also decreased significantly in the cerebellar microsomes of 25-day-old LMB and human OPCA when compared with their respective controls. These data indicate that the decrease of second messenger linked PKC activity and InsP3 receptor binding in CB may be a biochemical marker that reflects neuronal degeneration in dominant cerebellar ataxia.
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