α-Syn oligomers incubated with Parkinson's disease plasma promote neuron damage.

α-Syn oligomers incubated with Parkinson's disease plasma promote neuron damage. Int J Clin Exp Pathol. 2020;13(8):1995-2008 Authors: Yang W, Li X, Yin N Abstract Alpha-Synuclein (α-Syn) aggregates represent the major component of Lewy bodies (LBs), a pathologic hallmark of Parkinson's disease (PD). Current reports have assessed the toxicity of oligomeric α-Syn (o-α-Syn) mostly in vitro after the incubation with PBS, which leaves o-α-Syn non-phosphorylated and does not reflect actual physiologic conditions in PD patients. The present study aimed to assess the pathogenic role of o-α-Syn while addressing the above issues using o-α-Syn incubated with PD plasma. Several α-Syn oligomer types were prepared by incubating recombinant human α-Syn with phosphate-buffered saline (PBS), and plasma samples from normal controls (NS) and PD patients. O-α-Syn incubated with PD plasma (o-α-Syn-PD), moderately or highly phosphorylated at serine 129, induced cell death more substantially compared with the PBS and NS groups. PD plasma exhibited reduced PP2A activity and ceramide levels, promoting the phosphorylation of o-α-Syn. In agreement, ceramide addition alleviated o-α-Syn-PD cytotoxicity. In vivo, o-α-Syn-PD significantly reduced dopaminergic neurons in the substantia nigra and could be transferred to the cortex, hippocampus, and other parts of the brain. Mice administered o-α-Syn-PD exhibited significant PD-like dyskinesia changes ...
Source: International Journal of Clinical and Experimental Pathology - Category: Pathology Authors: Tags: Int J Clin Exp Pathol Source Type: research