Krabbe Disease: Isolation and Characterization of a Full-Length cDNA for Human Galactocerebrosidase

Sakai, Norio; Inui, Koji; Fujii, Nobutaka; Fukushima, Hisao; Nishimoto, Junji; Yanagihara, Itaru; Isegawa, Yuji; Iwamatsu, Akihiro; Okada, Shunichi

doi:10.1006/bbrc.1994.1071

Cited by 92 publications

(65 citation statements)

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“…1 Instead of CAAT or TATA boxes, the promoter region of the GALC gene demonstrated to have signal sequences susceptible to the transcription factors SP1 (5 0 -CCCGCC-3 0 ), YY1 (5 0 -AAA TGG-3 0 ) and AP2 (5 0 -GCCTGCAGGC-3 0 ). 1,14,17,18 Even though several groups were working on slightly different promoter regions, these findings were similar. 1,4,5,14 One approach to explain the decreased transcription of the GALC gene is to hypothesize that inhibiting transcription factors bind to an appropriate promoter region leading to decreased GALC transcription.…”

Section: Repression Of the Galc Gene Galc Promoter Region And Transcrmentioning

confidence: 63%

Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells

Beier

Görögh

2005

Intl Journal of Cancer

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Galactosylcerebroside is known to be overexpressed upon the cellular surface of a variety of cancers. In squamous cell carcinomas of the head and neck, one explanation for galactosylcerebroside accumulation has been identified as a transcriptional repression of the galactocerebrosidase gene. Galactocerebrosidase is the enzyme responsible for degrading galactosylcerebroside to ceramide. Ceramide is an important apoptosis activator, whereas galactosylcerebroside functions as an inhibitor. A shift of the ceramide metabolism balance in favor of glycosylated forms has been identified as a mechanism of drug resistance for several antineoplastic agents. Our review elaborates on possible explanations for galactocerebrosidase suppression and on other explanations for increased glycosphingolipid concentration within cancer cell membranes. Furthermore, conjecturable influences of a repressed galactocerebrosidase expression on tumor biology are to be explained. The inhibiting transcription factors YY1 and AP2 have been identified as potential galactocerebrosidase gene suppressors. The resulting accumulation of galactosylcerebroside promotes a reduction of cellular adhesion and inhibits apoptosis, leading to increased cellular growth, migration and prolonged cell survival contributing to carcinogenesis. ' 2005 Wiley-Liss, Inc.

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Section: Repression Of the Galc Gene Galc Promoter Region And Transcrmentioning

confidence: 63%

Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells

Beier

Görögh

2005

Intl Journal of Cancer

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“…10,11 Total RNA was extracted from primary human skin fibroblasts using RNeasy Kit (Qiagen, Hilden, Germany). RT-PCR was performed using RNA LA PCR kit (TaKaRa, Osaka, Japan).…”

Section: Galc Cdna Cloningmentioning

confidence: 99%

“…9 However, the disadvantages of BMT such as shortage in donor supply and the side-effects largely limit the clinical application of this treatment. With the success in the cloning of GALC cDNA and the identification of gene mutation in twitcher, [10][11][12] gene therapy of the twitcher mouse became possible and challenging.…”

Section: Introductionmentioning

confidence: 99%

Intraventricular administration of recombinant adenovirus to neonatal twitcher mouse leads to clinicopathological improvements

Watabe

Ohashi

et al. 2001

Gene Ther

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Twitcher mouse is a murine model of human globoid cell leukodystrophy (Krabbe disease), which is characterized by a genetic deficiency in galactocerebrosidase (GALC) activity. The nervous system is affected early and severely by demyelination in the white matter. So far, there is no effective treatment for Krabbe disease except bone marrow transplantation (BMT). However, BMT has inherent limitations such as unavailability of donors and graft-versus-host disease. In this study, we injected recombinant adenovirus encoding GALC into the lateral ventricle of twitcher mice at postnatal day 0 (PND 0) and the therapeutic effects were evaluated. Our results showed slight, but significant

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“…Its linear nucleotide sequence open reading frame is 2,058 nucleotides and has 45.92% GC content. Mutation analysis of the human GALC gene was facilitated by cloning [9] and sequencing of GALC cDNA [10,11]. The Human Gene Mutation Database (http://www.hgmd.org) reports over 130 variants in the GALC gene, which mostly associated with an affected phenotype.…”

Section: Identification Of Galc Mutation and Prediction Analysismentioning

confidence: 99%

Genetic Test and Gene Therapy for Krabbe Disease: An Update

Graziano

Cardile²

2014

Gene Technology

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Globoid cell leukodystrophy, also known as Krabbe disease, is an inherited metabolic neurodegenerative disease, due to genetic mutation of β-galactocerebrosidase gene. Here we reviewed how the technological advances in gene analysis have enhanced the enrichment of mutation database. Moreover, we focus on the possibility to develop genetic treatments, hoping that the updating of genetic, clinical and biochemical data will improve for an early and efficient diagnosis, until a definitive treatment option will be identified.

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Krabbe Disease: Isolation and Characterization of a Full-Length cDNA for Human Galactocerebrosidase

Cited by 92 publications

References 0 publications

Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells

Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells

Intraventricular administration of recombinant adenovirus to neonatal twitcher mouse leads to clinicopathological improvements

Genetic Test and Gene Therapy for Krabbe Disease: An Update

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