A novel mutation in the C2 domain of protein kinase C gamma associated with spinocerebellar ataxia type 14

Ueda, Takahiro; Seki, Tsuneyoshi; Katanazaka, Kimitaka; Sekiguchi, Kenji; Kobayashi, Kenzo; Kanda, Fumio; Toda, Tatsushi

doi:10.1007/s00415-013-6916-0

Cited by 6 publications

(4 citation statements)

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“…Several missense mutations in the PKCγ gene have been found in spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease (Yamamoto et al, 2010; Ueda et al, 2013). Mutant PKCγ kinases act as a dominant negative regulator on wild-type PKCγ enzymes, disrupting synaptic pruning, plasticity and transmission (Shuvaev et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma

Ménard

Bastianetto

Quirion

2013

Front. Cell. Neurosci.

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Polyphenols such as epigallocatechin gallate (EGCG) and resveratrol have received a great deal of attention because they may contribute to the purported neuroprotective action of the regular consumption of green tea and red wine. Many studies, including those published by our group, suggest that this protective action includes their abilities to prevent the neurotoxic effects of beta-amyloid, a protein whose accumulation likely plays a pivotal role in Alzheimer's disease. Moreover, the scavenging activities of polyphenols on reactive oxygen species and their inhibitory action of cyclooxygenase likely explain, at least in part, their antioxidant and anti-inflammatory activities. Besides these well-documented properties, the modulatory action of these polyphenols on intracellular signaling pathways related to cell death/survival (e.g., protein kinase C, PKC) has yet to be investigated in detail. Using rat hippocampal neuronal cells, we aimed to investigate here the effects of EGCG and resveratrol on cell death induced by GF 109203X, a selective inhibitor of PKC. The MTT/resazurin and spectrin assays indicated that EGCG and resveratrol protected against GF 109203X-induced cell death and cytoskeleton degeneration, with a maximal effect at 1 and 3 μM, respectively. Moreover, immunofluorescence data revealed that cells treated with these polyphenols increased PKC gamma (γ) activation and promoted neuronal interconnections. Finally, we found that the protective effects of both polyphenols on the cytoskeleton and synaptic plasticity were mediated by the PKCγ subunit. Taken together, the results suggest that PKC, and more specifically its γ subunit, plays a critical role in the protective action of EGCG and resveratrol on neuronal integrity.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma

Ménard

Bastianetto

Quirion

2013

Front. Cell. Neurosci.

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“…Many other mutations affect calcium and potassium ion channels (EA2, SCA6, EA1, EA5, SCA13, SCA19, SCA22) (Supplementary Material, Table S1 ) (Yue et al, 1997 ; Zhuchenko et al, 1997 ; Lin et al, 2000 ; Guida et al, 2001 ; Imbrici et al, 2003 ; Sausbier et al, 2004 ; Tonelli et al, 2006 ; Bürk et al, 2014 ) that are important for regulating the rate of calcium influx into cells. spinocerebellar ataxia 14 (SCA14) involves a mutation in the gene encoding protein kinase C (PKC) that is also important for calcium homeostasis (Supplementary Material, Figure S1A ; Table S1 ) (Alonso et al, 2005 ; Ueda et al, 2013 ; van Gaalen et al, 2013 ; Ji et al, 2014 ). spinocerebellar ataxia 15 (SCA15) and spinocerebellar ataxia 16 (SCA16) in humans and in mice are caused by deletion and missense mutations in the gene for inositol-1,4,5-trisphosphate receptor type 1 (IP3R1), a calcium channel on the sER (Desaiah et al, 1991 ; Street et al, 1997 ; Zecevic et al, 1999 ; Lin et al, 2000 ; Storey et al, 2001 ; Serra et al, 2004 ; van de Leemput et al, 2007 ; Chen et al, 2008 ; Chou et al, 2008 ; Hara et al, 2008 ; Iwaki et al, 2008 ; Liu et al, 2009 ; Di Gregorio et al, 2010 ; Novak et al, 2010a , b ; Huang et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Computational neurobiology is a useful tool in translational neurology: the example of ataxia

2015

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Hereditary ataxia, or motor incoordination, affects approximately 150,000 Americans and hundreds of thousands of individuals worldwide with onset from as early as mid-childhood. Affected individuals exhibit dysarthria, dysmetria, action tremor, and diadochokinesia. In this review, we consider an array of computational studies derived from experimental observations relevant to human neuropathology. A survey of related studies illustrates the impact of integrating clinical evidence with data from mouse models and computational simulations. Results from these studies may help explain findings in mice, and after extensive laboratory study, may ultimately be translated to ataxic individuals. This inquiry lays a foundation for using computation to understand neurobiochemical and electrophysiological pathophysiology of spinocerebellar ataxias and may contribute to development of therapeutics. The interdisciplinary analysis suggests that computational neurobiology can be an important tool for translational neurology.

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“…It was also reported in a 4th generation American family of English and Dutch origin who displayed pure cerebellar ataxia (Brkanac et al, 2002). SCA14 has also been reported in various countries such as Australia (Kang et al, 2019), Norway (Koht et al, 2012), Germany (Ganos et al, 2014), Japan (Ueda et al, 2013), and China (Chen et al, 2022). There is an ambiguous correlation between clinical manifestations and ethnicity, while the age of onset occurs between childhood and 60 years old.…”

Section: Introductionmentioning

confidence: 97%

“…Furthermore, Parkinson’s disease ( Sailer et al, 2012 ; Chen et al, 2022 ), which is characterized by muscle rigidity and tremors, has also been reported in some family pedigrees. Patients with SCA14 may exhibit further ataxic conditions such as dysphagia ( Ueda et al, 2013 ). The incidence of SCA14 is from 1% to 4% in all autosomal genetic disorders ( Chelban et al, 2018 ), and it was first reported in a Japanese family in 2000 ( Yamashita et al, 2000 ).…”

Section: Introductionmentioning

confidence: 99%

Novel mutation in exon11 of PRKCG (SCA14): A case report

Sun

Xiang²,

Cao³

et al. 2023

Front. Genet.

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Introduction:PRKCG mutations have been implicated in the pathogenesis of spinocerebellar ataxia type 14 (SCA14), which is a rare autosomal dominant disease marked by cerebellar degeneration, dysarthria, and nystagmus. Until now, there has never been a report of patients with mutations of c.1232G>C worldwide.Case description: We report a case of a 30-year-old Chinese man with episodic dystaxia, speech disorder, and cognitive impairment; however, his father exclusively exhibited a speech disorder regardless of the same mutation. Whole-exome sequencing revealed a heterozygous c.1232G>C (p.G411A) variant of PRKCG.Conclusion: This case presents an extended genotype and phenotype of SCA14, and emphasizes the importance of gene sequencing in patients with spinocerebellar ataxia.

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A novel mutation in the C2 domain of protein kinase C gamma associated with spinocerebellar ataxia type 14

Cited by 6 publications

References 6 publications

Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma

Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma

Computational neurobiology is a useful tool in translational neurology: the example of ataxia

Novel mutation in exon11 of PRKCG (SCA14): A case report

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