Approximately 90% of alpha-synuclein (α-Synuclein) deposited in Lewy bodies is phosphorylated at ... more Approximately 90% of alpha-synuclein (α-Synuclein) deposited in Lewy bodies is phosphorylated at serine 129 suggesting that the accumulation of phosphorylated α-Synuclein is critical in the pathogenesis of Parkinson’s disease. However, in vivo experiments addressing the role of phosphorylated α-Synuclein in the progression of Parkinson’s disease have produced equivocal data. To clarify a role of Ser129 phosphorylation of α-Synuclein in pathology progression we performed stereotaxic injections targeting the mouse striatum with three fibrilar α-Synuclein types: wt-fibrils, phosphorylated S129 fibrils and, phosphorylation incompetent, S129A fibrils. Brain inoculation of all three fibrilar types caused seeding of the endogenous α-Synuclein. However, phosphorylated fibrils triggered the formation of more α-Synuclein inclusions in the Substantia Nigra pars compacta (SNpc), exacerbated pathology in the cortex and caused dopaminergic neuronal loss and fine motor impairment as early as 60 da...
Approximately 90% of alpha-synuclein (α-Synuclein) deposited in Lewy bodies is phosphorylated at ... more Approximately 90% of alpha-synuclein (α-Synuclein) deposited in Lewy bodies is phosphorylated at serine 129 suggesting that the accumulation of phosphorylated α-Synuclein is critical in the pathogenesis of Parkinson’s disease. However, in vivo experiments addressing the role of phosphorylated α-Synuclein in the progression of Parkinson’s disease have produced equivocal data. To clarify a role of Ser129 phosphorylation of α-Synuclein in pathology progression we performed stereotaxic injections targeting the mouse striatum with three fibrilar α-Synuclein types: wt-fibrils, phosphorylated S129 fibrils and, phosphorylation incompetent, S129A fibrils. Brain inoculation of all three fibrilar types caused seeding of the endogenous α-Synuclein. However, phosphorylated fibrils triggered the formation of more α-Synuclein inclusions in the Substantia Nigra pars compacta (SNpc), exacerbated pathology in the cortex and caused dopaminergic neuronal loss and fine motor impairment as early as 60 da...
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