| Item type |
文献 / Documents(1) |
| 公開日 |
2020-09-16 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1016/j.bbrep.2016.04.012 |
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関連名称 |
10.1016/j.bbrep.2016.04.012 |
| 出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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タイトル |
Combined replacement effects of human modified β-hexosaminidase B and GM2 activator protein on GM2 gangliosidoses fibroblasts |
| 著者 |
キタカゼ, ケイスケ
タサキ, チカコ
タジマ, ヨウイチ
ヒロカワ, タカツグ
辻, 大輔
サクラバ, ヒトシ
伊藤, 孝司
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| 抄録 |
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内容記述 |
GM2 gangliosidoses are autosomal recessive lysosomal storage diseases (LSDs) caused by mutations in the HEXA, HEXB and GM2A genes, which encode the human lysosomal β-hexosaminidase (Hex) α- and β-subunits, and GM2 activator protein (GM2A), respectively. These diseases are associated with excessive accumulation of GM2 ganglioside (GM2) in the brains of patients with neurological symptoms. Here we established a CHO cell line overexpressing human GM2A, and purified GM2A from the conditioned medium, which was taken up by fibroblasts derived from a patient with GM2A deficiency, and had the therapeutic effects of reducing the GM2 accumulated in fibroblasts when added to the culture medium. We also demonstrated for the first time that recombinant GM2A could enhance the replacement effect of human modified HexB (modB) with GM2-degrading activity, which is composed of homodimeric altered β-subunits containing a partial amino acid sequence of the α-subunit, including the GSEP loop necessary for binding to GM2A, on reduction of the GM2 accumulated in fibroblasts derived from a patient with Tay-Sachs disease, a HexA (αβ heterodimer) deficiency, caused by HEXA mutations. We predicted the same manner of binding of GM2A to the GSEP loop located in the modified HexB β-subunit to that in the native HexA α-subunit on the basis of the x-ray crystal structures. These findings suggest the effectiveness of combinational replacement therapy involving the human modified HexB and GM2A for GM2 gangliosidoses. |
| キーワード |
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主題 |
Lysosomal storage disease |
| キーワード |
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|
主題 |
Gm2 gangliosidosis |
| キーワード |
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|
主題 |
Gm2 activator protein |
| キーワード |
|
|
主題 |
β-hexosaminidase |
| キーワード |
|
|
主題 |
Enzyme replacement therapy |
| 書誌情報 |
en : Biochemistry and Biophysics Reports
巻 7,
p. 157-163,
発行日 2016-06-08
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
24055808 |
| 出版者 |
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出版者 |
Elsevier |
| 権利情報 |
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|
権利情報 |
© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| EID |
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|
識別子 |
333867 |
| 言語 |
|
|
言語 |
eng |
bbrep_7_157.pdf (1.31 MB)
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