biostudies-literatureZhao JNational Institute of Neurological Disorders and StrokeNIA NIH HHSNCRR NIH HHSNINDS NIH HHSNational Institutes of HealthNational Institute of General Medical SciencesNIH HHSNIGMS NIH HHSNational Science Foundation20https://www.ebi.ac.uk/biostudies/studies/S-EPMC8991655biostudies-literatureUnknown11(1)<h4>Background</h4>Alpha-synuclein (α-syn) exhibits pathological misfolding in many human neurodegenerative disorders. We previously showed that α-syn is arginylated in the mouse brain and that lack of arginylation leads to neurodegeneration in mice.<h4>Methods</h4>Here, we tested α-syn arginylation in human brain pathology using newly derived antibodies in combination with Western blotting, biochemical assays, and experiments in live neurons.<h4>Results</h4>We found that α-syn was arginylated in the human brain on E46 and E83, two sites previously implicated in α-syn pathology and familial cases of Parkinson's disease. The levels of arginylation in different brain samples ranged between ~ 3% and ~ 50% of the total α-syn pool, and this arginylation nearly exclusively concentrated in the suTranslational neurodegenerationα-Synuclein arginylation in the human brain.PMC8991655R01NS102435U19 AG062418S10 RR023444RR-023444R35GM122505R01 NS120625R01NS120625CHE-1827457R35 GM122505R01 NS102435MRI-0820996P30 AG072979Dong DWHuang YLuk KCShimogawa MPetersson EJPan BKashina AZhao JFina MRhoades Efalseα-Synuclein arginylation in the human brain.<h4>Background</h4>Alpha-synuclein (α-syn) exhibits pathological misfolding in many human neurodegenerative disorders. We previously showed that α-syn is arginylated in the mouse brain and that lack of arginylation leads to neurodegeneration in mice.<h4>Methods</h4>Here, we tested α-syn arginylation in human brain pathology using newly derived antibodies in combination with Western blotting, biochemical assays, and experiments in live neurons.<h4>Results</h4>We found that α-syn was arginylated in the human brain on E46 and E83, two sites previously implicated in α-syn pathology and familial cases of Parkinson's disease. The levels of arginylation in different brain samples ranged between ~ 3% and ~ 50% of the total α-syn pool, and this arginylation nearly exclusively concentrated in the su2022-01-01T00:00:00Z2022 Apr2025-04-22T03:57:47.183Z2025-04-05T20:49:22.923ZS-EPMC89916553539595610.1186/s40035-022-00295-0