• Molecules and Cells
• /
• v.27 no.6
• /
• pp.621-627
• /
• 2009

Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder characterized by ataxia and progressive motor deterioration. SCA1 is associated with an elongated polyglutamine tract in ataxin-1, the SCA1 gene product. As summarized in this review, recent studies have clarified the molecular mechanisms of SCA1 pathogenesis and provided direction for future therapeutic approaches. The nucleus is the subcellular site where misfolded mutant ataxin-1 acts to cause SCA1 disease in the cerebellum. The role of these nuclear aggregates is the subject of intensive study. Additional proteins have been identified, whose conformational alterations occurring through interactions with the polyglutamine tract itself or non-polyglutamine regions in ataxin-1 are the cause of SCA-1 cytotoxicity. Therapeutic hope comes from the observations concerning the reduction of nuclear aggregation and alleviation of the pathogenic phenotype by the application of potent inhibitors and RNA interference.

• Journal of Life Science
• /
• v.21 no.5
• /
• pp.671-677
• /
• 2011

We previously reported the isolation and characterization of a gene, SCA1 (for soybean $Ca^{2+}$-ATPase 1), encoding a calmodulin-regulated $Ca^{2+}$-ATPase that is located in the plasma membrane in soybean. Here, a $Ca^{2+}$-ATPase designated as SCA2 was isolated from soybean. The two $Ca^{2+}$-ATPases, SCA1 and SCA2, share a remarkably high degree of similarity (78%). Ten transmemebrane domains were predicted by hydropathy analysis. Using gel overlay assays, CaM was found to bind to SCA2 in a $Ca^{2+}$-dependent manner. Southern blot analysis revealed the presence of two copies of the $Ca^{2+}$-ATPase gene in the soybean genome. An N-terminal truncation mutant that deletes sequence through the putative calmodulin binding site was able to complement a yeast mutant (K616) that was deficient in two endogenous $Ca^{2+}$ pumps. Our results indicate that SCA2 is structurally highly conserved with type IIB $Ca^{2+}$ pumps in plants.

• Journal of Genetic Medicine
• /
• v.4 no.1
• /
• pp.22-37
• /
• 2007

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases, clinically and genetically heterogeneous, characterized by degeneration of spinocerebellar pathways with variable involvement of other neural systems. At present, 27 distinct genetic forms of SCAs are known: SCA1-8, SCA10-21, SCA23, SCA25-28, DRPLA (dentatorubral-pallidoluysian atrophy), and 16q-liked ADCA (autosomal dominant cerebellar ataxia). Epidemiological data about the prevalence of SCAs are restricted to a few studies of isolated geographical regions, and most do not reflect the real occurrence of the disease. In general a prevalence of about 0.3-2 cases per 100,000 people is assumed. As SCA are highly heterogeneous, the prevalence of specific subtypes varies between different ethnic and continental populations. Most recent data suggest that SCA3 is the commonest subtype worldwide; SCA1, SCA2, SCA6, SCA7, and SCA8 have a prevalence of over 2%, and the remaining SCAs are thought to be rare (prevalence <1%). In this review, we highlight and discuss the SCA7. The hallmark of SCA7 is the association of hereditary ataxia and visual loss caused by pigmentary macular degeneration. Visual failure is progressive, bilateral and symmetrical, and leads irreversibly to blindness. This association represents a distinct disease entity classified as autosomal dominant cerebellar ataxia (ADCA) type II by Harding. The disease affectsprimarily the cerebellum and the retina by the moderate to severe neuronal loss and gliosis, but also many other central nervous system structures as the disease progresses. SCA7 is caused by expansion of an unstable trinucleotide CAG repeat in the ATXN7 gene encoding a polyglutamine (polyQ) tract in the corresponding protein, ataxin-7. Normal ATXN7 alleles contain 4-35 CAG repeats, whereas pathological alleles contain from 36->450 CAG repeats. Immunoblott analysis demonstrated that ataxin-7 is widely expressed but that expression levels vary among tissues. Instability of expanded repeats is more pronounced in SCA7 than in other SCA subtypes and can cause substantial lowering of age at onset in successive generations termed ‘anticipation’ so that children may become diseased even before their parents develop symptoms. The strong anticipation in SCA7 and the rarity of contractions should have led to its extinction within a few generations. There is no specific drug therapy for this neurodegenerative disorder. Currently, therapy remains purely symptomatic. Cellular models and SCA7 transgenic mice have been generated which constitute valuable resources for studying the disease mechanism. Understanding the pathogenetic mechanisms of neurodegeneration in SCAs should lead to the identification of potential therapeutic targets and ultimately facilitate drug discovery. Here we summarize the clinical, pathological, and genetic aspects of SCA7, and review the current understanding of the pathogenesis of this disorder. Further, we also review the potential therapeutic strategies that are currently being explored in polyglutamine diseases.

• Journal of Life Science
• /
• v.16 no.1
• /
• pp.76-81
• /
• 2006

A $\gamma-butyrolactone$ autoregulator receptor has a common activity as DNA-binding transcriptional repressors controlling secondary metabolism and/or morphological differentiation in Streptomyces. A gene (scaR) encoding it was cloned from Streptomyces cravuligerus, a clavulanic acid producer, and was in vitro characterized in a previous report. In this study to clarify the in vivo function of ScaR, a $\gamma-butyrolactone$ autoregulator receptor of Streptomyces clavuligerus, we constructed a scaR-deleted strain by means of homologous recombination. No difference in morphology was found between the wild-type strain and the scaR-disruptant, but the scaR-disruptant showed higher clavulanic acid production. This indicates that the ScaR in S. clavuligerus acts as a negative regulator of the biosynthesis of clavulanic acid, but plays no role in morphological differentiation.

• Molecules and Cells
• /
• v.19 no.1
• /
• pp.23-30
• /
• 2005

Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder caused by expansion of the polyglutamine tract in the SCA1 gene product, ataxin-1. Using d2EGFP, a short-lived enhanced green fluorescent protein, we investigated whether polyglutamine-expanded ataxin-1 affects the function of the proteasome, a cellular multicatalytic protease that degrades most misfolded proteins and regulatory proteins. In Western blot analysis and immunofluorescence experiments, d2EGFP was less degraded in HEK 293T cells transfected with ataxin-1(82Q) than in cells transfected with lacZ or empty vector controls. To test whether the stability of the d2EGFP protein was due to aggregation of ataxin-1, we constructed a plasmid carrying $ataxin-1-{\Delta}114$, lacking the self-association region (SAR), and examined degradation of the d2EGFP. Both the level of $ataxin-1-{\Delta}114$ aggregates and the amount of d2EGFP were drastically reduced in cells containing $ataxin-1-{\Delta}114$. Furthermore, d2EGFP localization experiments showed that polyglutamine-expanded ataxin-1 inhibited the general function of the proteasome activity. Taken together, these results demonstrate that polyglutamine-expanded ataxin-1 decreases the activity of the proteasome, implying that a disturbance in the ubiquitin-proteasome pathway is directly involved in the development of spinocerebellar ataxia type1.

• The Journal of Internal Korean Medicine
• /
• v.42 no.5
• /
• pp.784-792
• /
• 2021

Objectives: The purpose of this study was to investigate a case of a patient with spinocerebellar ataxia (SCA) type 2 whose condition improved following treatment with Korean medicine. Methods: A 25-year-old man, diagnosed with SCA type 2, was treated with herbal medicine (Yukmijiwhang-tang-gami), acupuncture, and physical treatment. The therapeutic effect was evaluated using the Berg Balance Scale (BBS) and gait status. Results: Following treatment, the BBS score increased, and gait ataxia improved. Conclusions: This case study suggests that Korean medicine could be effective for relieving symptoms of SCA type 2.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.27 no.6
• /
• pp.842-846
• /
• 2013

The purpose of this study was to report one clinical case of spinocerebellar ataxia(SCA) type 1 improved by herbal medicine and oriental medical treatment. As a treatment, Yukmijihwang-tang(Liuweidihuangtang)-gamibang, acupuncture, and moxa were tried upon the patient for 21 days in order to relieve the symptoms. In terms of observing the changes of symptoms, the progress of patient's condition was evaluated periodically by using the Korean-mini mental state examination(K-MMSE), Modified Barthel Index(MBI), Functional Independence Measure(FIM). In accordance with the observation under K-MMSE, MBI, FIM, the patient's symptoms had gradually improved throughout the treatment. Therefore, this report suggests that Yukmijihwang-tang(Liuweidihuangtang)-gamibang, acupuncture and moxa were probably effective in the treatment of SCA type 1.

• Annals of Clinical Neurophysiology
• /
• v.9 no.2
• /
• pp.102-104
• /
• 2007

Spinocerebellar ataxia type 2 (SCA2) is characterized by progressive cerebellar ataxia and slow saccades. A 40-year-old woman presented with progressive gait disturbance and ataxia over 15 years. Neurologic examination revealed scanning speech, ataxia, and hyporeflexia. Brain CT showed diffuse atrophy of the cerebellum. Electronystagmography demonstrated slowed saccades with normal accuracy and delayed latency. The diagnosis of SCA2 was confirmed by the genetic test. Documentation of slow saccades may help differentiation among SCA subgroups.

• KOREAN JOURNAL OF CROP SCIENCE
• /
• v.51 no.7
• /
• pp.652-657
• /
• 2006

Combining ability and heterosis for $F_{1}$ population obtained $5{\times}5$ half diallel cross in sesame were estimated for six quantitative characters. The parental varieties used for diallel cross were Yangbaek and Ansan of normal type, Suwon 177 and 195 of placenta adhesion type (PA) and SIG960320-5-1-1 of indehiscent type (ID). PA and ID type are shattering-resistant sesames and Yangbaek and Ansan are shattering sesames. The high heterosis of $F_{1}$ hybrids was expressed in the number of capsules per plant (NC), grain yield per plant (GY) and number of branches per plant (NB). Shattering.ate (SR) showed high positive heterosis toward increase of seeds shattering in all the combination of $F_{1}$ generation which was presumed because the characters connected with shattering resistance of seeds were governed by recessive gene. At the analysis of combining ability, highly significant general combining ability (GCA) effects were observed on all the characters in $F_{1}$ generation, significant specific combining ability (SCA) effects were observed on the NC, GY and SR. GCA variances were greater than SCA variance, which suggested that additive gene effects were greater than other nonadditive gene effects. Considering the estimated GCA effects, Suwon 195 (PA type) was found to be good parent for SR and GY, SIG960320-5-1-1 (ID type) was poor for GY and plant height. SCA effect for NC was great in Yangbaek/Suwon 195, SCA for GY was great in Ansan/SIG960320-5-1-1, and SCA for decrease of SR was great in Ansan/Suwon177.

• The Journal of Internal Korean Medicine
• /
• v.37 no.2
• /
• pp.322-329
• /
• 2016

Objective: This study reports on one clinical case of type 3 spinocerebellar ataxia (SCA) to examine the effectiveness of herbal medicine and traditional Korean treatments.Methods: A patient with type 3 spinocerebellar ataxia was treated using traditional Korean medicine options such as acupuncture and Hyangsayukgunja-tang. The effects on type 3 spinocerebellar ataxia were measured using the numeric rating scale (NRS) and ambulatory status.Results: Improvements in NRS and ambulatory status were observed after treatment.Conclusion: According to this study, traditional Korean medicine may be effective in the treatment of type 3 spinocerebellar ataxia.