The formation of highly soluble oligomers of α-synuclein is regulated by fatty acids and enhanced in Parkinson's disease

被引：469

作者：

Sharon, R ^{[1
]}

Bar-Joseph, I ^{[1
]}

Frosch, MP ^{[1
]}

Walsh, DM ^{[1
]}

Hamilton, JA ^{[1
]}

Selkoe, DJ ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02215 USA

来源：

NEURON | 2003年 / 37卷 / 04期

关键词：

D O I：

10.1016/S0896-6273(03)00024-2

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Accumulation of misfolded proteins as insoluble aggregates occurs in several neurodegenerative diseases. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), alpha-synuclein (alphaS) accumulates in insoluble inclusions. To identify soluble alphaS oligomers that precede insoluble aggregates, we probed the cytosols of mesencephalic neuronal (MES) cells, normal and alphaS-transgenic mouse brains, and normal, PD, and DLB human brains. All contained highly soluble oligomers; of alphaS whose detection was enhanced by delipidation. Exposure of living MES neurons to polyunsaturated fatty acids (PUFAs) increased alphaS oligomer levels, whereas saturated FAs decreased them. PUFAs directly promoted oligomerization of recombinant alphaS. Transgenic mice accumulated soluble oligomers with age. PD and DLB brains had elevated amounts of the soluble, lipid-dependent oligomers. We conclude that alphaS interacts with PUFAs in vivo to promote the formation of highly soluble oligomers that precede the insoluble alphaS aggregates associated with neurodegeneration.

引用

页码：583 / 595

页数：13

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