Baicalein inhibits α-synuclein oligomer formation and prevents progression of α-synuclein accumulation in a rotenone mouse model of Parkinson's disease
Biochim Biophys Acta. 2016 Jul 15;1862(10):1883-1890. doi: 10.1016/j.bbadis.2016.07.008. [Epub ahead of print]
|Authors/Editors:||Hu Q, Uversky VN, Huang M, Kang H, Xu F, Liu X, Lian L, Liang Q, Jiang H, Liu A, Zhang C, Pan-Montojo F, Zhu S|
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.