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您的检索式：作者名="David I.Finkelstein"
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| 1 | Pharmacological inhibition of FABP7 by MF 6 counteracts cerebellum dysfunction in an experimental multiple system atrophy mouse model显示文摘Multiple system atrophy(MSA)is a rare,fatal neurodegenerative disease characterized by the accumulation of misfolded asynuclein(asyn)in glial cells,leading to the formation of glial cytoplasmic inclusions(GCl).We previous found that glial fatty acidbinding protein 7(FABP7)played a crucial role in alpha-synuclein(aSyn)aggregation and toxicity in oligodendrocytes,inhibition of FABP7 by a specific inhibitor MF 6 reduced aSyn aggregation and enhanced cell viability in cultured cell lines and mouse oligodendrocyte progenitor cells.In this study we investigated whether MF 6 ameliorated aSyn-associated pathological processes in PLP-haSyn transgenic mice(PLP-aSyn mice),a wildly used MSA mouse model with overexpressing aSyn in oligodendroglia under the proteolipid protein(PLP)promoter.PLP-aSyn mice were orally administered MF6(0.1,1 mg·kg^(-1)·d^(-1))for 32 days starting from the age of 6 months.We showed that oral administration of MF 6 significantly improved motor function assessed in a pole test,and reduced aSyn aggregation levels in both cerebellum and basal ganglia of PLP-aSyn mice.Moreover,MF 6 administration decreased oxidative stress and inflammation levels,and improved myelin levels and Purkinje neuron morphology in the cerebellum.By using mouse brain tissue slices and aSyn aggregates-treated KG-1C cells,we demonstrated that MF 6 reduced aSyn propagation to Purkinje neurons and oligodendrocytes through regulating endocytosis.Overall,these results suggest that MF 6 improves cerebellar functions in MSA by inhibiting asyn aggregation and propagation.We conclude that MF 6 is a promising compound that warrants further development for the treatment of MSA. | An Cheng Wenbin Jia David I.Finkelstein Nadia Stefanova Haoyang Wang Takuya Sasaki Ichiro Kawahata Kohji Fukunaga | 2024 | Acta Pharmacologica Sinica2024，45，1： | 0 |
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