?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.title=Pathological+relevance+of+post-translationally+modified+alpha-synuclein+(pSer87%2C+pSer129%2C+nTyr39)+in+idiopathic+Parkinson%E2%80%99s+disease+and+Multiple+System+Atrophy&rft.creator=Sonustun%2C+B&rft.creator=Altay%2C+F&rft.creator=Strand%2C+C&rft.creator=Hondhamuni%2C+G&rft.creator=Warner%2C+T&rft.creator=Lashuel%2C+H&rft.creator=Bandopadhyay%2C+R&rft.description=Aggregated+alpha-synuclein+(a-synuclein)+is+the+main+component+of+Lewy+bodies+(LBs)%2C+Lewy+neurites+(LNs)%2C+and+glial+cytoplasmic+inclusions+(GCIs)%2C+which+are+pathological+hallmarks+of+idiopathic+Parkinson%E2%80%99s+disease+(IPD)+and+multiple+system+atrophy+(MSA)%2C+respectively.+Initiating+factors+that+culminate+in+forming+LBs%2FLNs%2FGCIs+remain+elusive.+Several+species+of+a-synuclein+exist%2C+including+phosphorylated+and+nitrated+forms.+It+is+unclear+which+a-synuclein+post-translational+modifications+(PTMs)+appear+within+aggregates+throughout+disease+pathology.+Herein+we+aimed+to+establish+the+predominant+a-synuclein+PTMs+in+post-mortem+IPD+and+MSA+pathology+using+immunohistochemistry.+We+examined+the+patterns+of+three+a-synuclein+PTMs+(pS87%2C+pS129%2C+nY39)+simultaneously+in+pathology-+affected+regions+of+15+PD%2C+5+MSA%2C+6+neurologically+normal+controls.+All+antibodies+recognized+LBs%2C+LNs%2C+and+GCIs%2C+albeit+to+a+variable+extent.+pS129+a-synuclein+antibody+was+particularly+immunopositive+for+LNs+and+synaptic+dot-like+structures+followed+by+nY39+a-+synuclein+antibody.+GCIs%2C+neuronal+inclusions%2C+and+small+threads+were+positive+for+nY39+a-+synuclein+in+MSA.+Quantification+of+the+LB+scores+revealed+that+pS129+a-synuclein+was+the+dominant+and+earliest+a-synuclein+PTM+followed+by+nY39+a-synuclein%2C+while+lower+amounts+of+pSer87+a-synuclein+appeared+later+in+disease+progression+in+PD.+These+results+may+have+implications+for+novel+biomarker+and+therapeutic+developments.&rft.subject=alpha-synuclein%3B+post-translational+modifications%3B+Parkinson%E2%80%99s+disease%3B+Multiple%0D%0Asystem+atrophy%3B+Lewy+bodies%3B+Lewy+neurites%3B+Glial+cytoplasmic+inclusions%3B+phosphorylation%3B%0D%0Anitration%3B+immunohistochemistry&rft.publisher=BioRXiv&rft.date=2022-01&rft.type=Working+%2F+discussion+paper&rft.language=eng&rft.source=++++BioRXiv%3A+Cold+Spring+Harbor%2C+NY%2C+USA.+(2022)+++++&rft.format=text&rft.identifier=https%3A%2F%2Fdiscovery.ucl.ac.uk%2Fid%2Feprint%2F10142175%2F1%2FBIORXIV-2022-475823v1-Bandopadhyay.pdf&rft.identifier=https%3A%2F%2Fdiscovery.ucl.ac.uk%2Fid%2Feprint%2F10142175%2F&rft.rights=open