Alpha-synuclein mutations impair axonal regeneration in models of Parkinson's disease.
作者： Lars Tönges , Éva M. Szegö , Patrizia Hause , Kim-Ann Saal , Lars Tatenhorst
关键词: Regeneration (biology) 、 Alpha-synuclein 、 Biology 、 Neuroscience 、 Signal transduction 、 Viral vector 、 Parkinson's disease 、 Rho-associated protein kinase 、 Lesion 、 Dopaminergic
摘要: The dopaminergic (DAergic) nigrostriatal tract has an intrinsic regenerative capacity which can be impaired in Parkinson’s disease (PD). Alpha-synuclein (aSyn) is a major pathogenic component PD but its impact on DAergic axonal regeneration largely unknown. In this study, we expressed variants of human aSyn by means recombinant adeno-associated viral vectors experimental paradigms regeneration. scratch lesion model vitro, both aSyn(A30P) and aSyn(A53T) significantly reduced neurite induced loss TH-immunopositive cells while aSyn(WT) showed only minor cellular neurotoxic effects. striatal density axons the 6-OHDA mouse was attenuated aSyn(A30P). However, expression levels marker GAP-43 fibers were aSyn(A53T), not associated with activation ROCK signaling pathway. Nigral cell mildly enhanced additional overexpression variants. Our findings indicate that mutations have strong neurons, may contribute to their
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