Enzymatic O-GlcNAcylation of α-synuclein reduces aggregation and increases SDS-resistant soluble oligomers
Enzymatic O-GlcNAcylation of α-synuclein reduces aggregation and increases SDS-resistant soluble oligomers
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α-突触核蛋白的酶促 O-GlcNAc 酰化可减少聚集并增加 SDS 抗性可溶性低聚物
DOI:
10.1016/j.neulet.2017.06.034
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发表时间:
2017-08
影响因子:
2.5
通讯作者:
Jia-Da Li
中科院分区:
文献类型:
--
作者:
Jiaming Zhang;Haozhi Lei;Yubei Chen;Yan-Tao Ma;Fang Jiang;Jieqiong Tan;Yi Zhang;Jia-Da Li
Neurodegenerative diseases including dementia with Lewy bodies, Lewy body variant of Alzheimer’s disease, and Parkinson’s disease are associated with the aberrant aggregation of α-synuclein, which is influenced by several post-translational modifications (PTMs).O-GlcNAcylation is one PTM that has an important role in many fundamental processes. TheO-GlcNAcylation of endogenous α-synuclein at residues 53, 64, 72 and 87 has been reported in an unbiased mass spectrum analysis. The consequences ofO-GlcNAcylation at residues 72 or 87 have been studied by using a synthetic α-synuclein bearingO-GlcNAcylation at threonine residue 72 or serine 87, respectively.O-GlcNAcylation at Thr72 or Ser87 suppresses the aggregation of α-synuclein. However, the effect of enzymaticO-GlcNAcylation of α-synuclein at multiple residues is not clear. Here, we successfully generatedO-GlcNAcylated α-synuclein by co-expressing a shorter form of OGT (sOGT) with α-synuclein. TheO-GlcNAcylation inhibited α-synuclein aggregation and promoted the formation of soluble SDS-resistant and Thioflavine T negative oligomers. Our data warrant further studies on the role ofO-GlcNAcylation in the progression/treatment of Parkinson’s disease in animal models.
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影响因子:
14.5
作者:
Paleologou, Katerina E.;Kragh, Christine L.;El-Agnaf, Omar M. A.
通讯作者:
El-Agnaf, Omar M. A.
DOI:
10.1073/pnas.1200425109
发表时间:
2012-05-08
影响因子:
11.1
作者:
Alfaro, Joshua F.;Gong, Cheng-Xin;Smith, Richard D.
通讯作者:
Smith, Richard D.
影响因子:
2.5
作者:
Dalfo, Esther;Martinez, Anna;Ferrer, Isidre
通讯作者:
Ferrer, Isidre
影响因子:
4
作者:
Lewis YE;Galesic A;Levine PM;De Leon CA;Lamiri N;Brennan CK;Pratt MR
通讯作者:
Pratt MR
影响因子:
21.8
作者:
Marotta NP;Lin YH;Lewis YE;Ambroso MR;Zaro BW;Roth MT;Arnold DB;Langen R;Pratt MR
通讯作者:
Pratt MR