• Journal of Microbiology and Biotechnology
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• v.8 no.6
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• pp.663-668
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• 1998

Several neurodegenerative diseases such as Huntington's disease, dentatorubralpallidoluysian atrophy, spinobulbar muscular atrophy, Machado-Joseph disease, and spinocerebellar ataxias type 1 are associated with the aggregation of expanded glutamine repeats within their proteins. Generally, in clinically affected individuals, the expansion of the polyglutamine sequences is beyond 40 residues. To address the length of polyglutamine that forms aggregation, we have constructed plasmids encoding glutathione S-transferase (GST) Machado-Joseph disease gene fusion proteins containing polyglutamine and investigated the formation of aggregates in E. coli. Surprisingly, even $(Gin)_8$, in the normal range as well as $(Gin)_{65}$ in the pathogenic range enhanced the formation of insoluble protein aggregates, whereas $(Ser)_8$, and $(Aia)_8$, did not form aggregates. Our results indicate that the formation of protein aggregates in GST-polyglutamine proteins is specifically mediated by the polyglutamine repeat sequence within their protein structure. Our study may contribute to the understanding of the molecular mechanism of the formation of protein aggregates in neurodegenerative disorders and the development of preventative strategies.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.84-87
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• 2007

Spinocerebellar Ataxia Type 3 (SCA 3) is a rare autosomal dominative disorder in which one of the neurodegenerative disorders is caused by a CAG repeat expansion on chromosome 14q32.1. The age at onset of disease is related to the size of the expanded CAG repeat. We present the prenatal diagnosis of SCA3 in a woman whose husband was known to carry an unstable CAG repeat expansion in the MJD gene. The diagnosis was made using PCR with a fluorescent probe for an expanded MJD allele. The normal ranges of (CAG)n of SCA3 are 14~38 repeats. The husband, who had a family history of SCA 3, has an expanded allele of 69 CAG repeats with a normal allele of 27 repeats. His wife had two normal alleles with 26 and 32 CAG repeats. The fetus had two normal alleles with 26 and 27 CAG repeats; consequently, the baby w as healthy. We report a case of prenatal diagnosis of SCA3 using a fluorescent PCR which is rapid and accurate.

• Clinical and Experimental Pediatrics
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• v.48 no.4
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• pp.425-432
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• 2005

Purpose : Polyglutamine diseases are a group of diseases caused by the expansion of a polyglutamine tract in the protein. The present study was performed to verify if polyglutamine disease transgenic Drosophila models show similar dysfunctions as are seen in human patients. Methods : Polyglutamine disease transgenic Drosophila were tested for their climbing ability. And using genetic methods, the effects of anti-apoptotic gene bcl-2 and chemical chaperones on neurodegeneration were observed. Also, spinocerebellar ataxia 2 (SCA2) transgenic Drosophila lines were generated for future studies. Results : Expanded forms of spinocerebellar ataxia 3 (SCA3) transgenic protein causes characteristic locomotor dysfunction when expressed in the nervous system of Drosophila but the anti-apoptotic gene bcl-2 shows no evidence of ameliorating the deleterious effect of the expanded protein. However, Glycerol, a chemical chaperone, seemed to reduce the toxicity, at least in the eyes of the transgenic flies. The level SCA2 expression is too weak in the transgenic SCA2 Drosophila for evaluation. Conclusion : SCA3 transgenic Drosophila show ataxic behavior as observed in human patients. Chemical chaperones such as glycerol may prove beneficial in this class of genetic disease, which has no current method of cure.