Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8258980 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2016 | 8 Pages |
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disease. α-Synuclein (α-syn) oligomers play a critical role in the progression of PD. Baicalein, a typical flavonoid compound, can inhibit the formation of the α-syn oligomers, and disaggregate existing α-syn oligomers in vitro. However, whether baicalein could inhibit or disaggregate α-syn oligomers in vivo has not been investigated. Therefore, this study was designed to investigate the inhibitory effects of baicalein on α-syn oligomers in vivo and to explore the possible mechanisms of such inhibition. A chronic PD mouse model was created by continuous intragastric administration of rotenone (5 mg/kg, 12 weeks). Baicalein (100 mg/kg) was intraperitoneally injected from 7 week to 12 week. Our result showed that the amount of α-syn, changes in the levels of the striatal neurotransmitters, and the behavioral changes found in the chronic PD mouse model were prevented after the baicalein injections. Although baicalein did not decrease α-syn mRNA expression, α-syn oligomers were significantly decreased in the ileum, thoracic spinal cord, and midbrain. Furthermore, transmission electron microscopy analysis showed that baicalein could prevent α-syn monomers from the oligomer formation in vitro. Taken together, these results suggest that baicalein could prevent the progression of α-syn accumulation in PD mouse model partly by inhibiting formation of the α-syn oligomers.
Keywords
PBSbaicaleinENSautophagy-lysosome pathwayDOPACIMLPFAα-SynLBSGAPDH3,4-dihydroxyphenylacetic acidDMSOα-synucleinALPEDTAEthylenediaminetetraacetic acidγ-aminobutyric acidsodium dodecyl sulfate-polyacrylamide gel electrophoresisSDS-PAGEstandard deviationTemLewy bodiesNeurodegenerative diseaseParkinson diseaseParkinson's diseasesubstantia nigratyrosine hydroxylaseDopamineDimethylsulfoxideRotenoneUbiquitin-proteasome systementeric nervous systemPhosphate buffered salineFlavonoidhomovanillic acidparaformaldehydeChATHVAhigh performance liquid chromatographyHPLCcholine acetyltransferaseGABAAglyceraldehyde-3-phosphate dehydrogenaseUPS
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Authors
Qi Hu, Vladimir N. Uversky, Mengyang Huang, Huicong Kang, Feng Xu, Xiaoyan Liu, Lifei Lian, Qiming Liang, Hong Jiang, Anding Liu, Cuntai Zhang, Francisco Pan-Montojo, Suiqiang Zhu,