Enzymatic O-GlcNAcylation of α-synuclein reduces aggregation and increases SDS-resistant soluble oligomers.
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| Abstract |
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. The O-GlcNAcylation of endogenous α-synuclein at residues 53, 64, 72 and 87 has been reported in an unbiased mass spectrum analysis. The consequences of O-GlcNAcylation at residues 72 or 87 have been studied by using a synthetic α-synuclein bearing O-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 enzymatic O-GlcNAcylation of α-synuclein at multiple residues is not clear. Here, we successfully generated O-GlcNAcylated α-synuclein by co-expressing a shorter form of OGT (sOGT) with α-synuclein. The O-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 of O-GlcNAcylation in the progression/treatment of Parkinson's disease in animal models.
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| Authors | Jiaming Zhang, Haozhi Lei, Yubei Chen, Yan-Tao Ma, Fang Jiang, Jieqiong Tan, Yi Zhang, Jia-Da Li |
| Journal | Neuroscience letters (Neurosci Lett) Vol. 655 Pg. 90-94 (Aug 10 2017) ISSN: 1872-7972 [Electronic] Ireland |
| PMID | 28673834 (Publication Type: Journal Article) |
| Copyright | Copyright © 2017 Elsevier B.V. All rights reserved. |
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