??synuclein abnormalities trigger focal tau pathology, spreading to various brain areas in Parkinson disease

Parkinson disease (PD) is the second most common neurodegenerative disorder, whose prevalence 2~3% in population over 65. ?-Synuclein aggregation major pathological hallmark of PD. However, recent studies have demonstrated enhancing evidence tau pathology Despite extensive considerations, thus far, actual spreading mechanism neurodegeneration has remained elusive a PD brain. This study aimed to further investigate development ?-synuclein and pathology. We employed various models, including cultured neurons treated with either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or recombinant ?-synuclein. Also, we studied dopaminergic cytokine Interferon-? knock-out. Moreover, examined rats 6-hydroxydopamine, Rhesus monkeys administrated MPTP neurotoxin, finally, human post-mortem brains. found phosphorylation triggers pathogenicity. observed more widespread phosphorylated than prion-like nature brain areas. optionally removed P-tau P-?-synuclein from interferon-? knock out respective monoclonal antibodies. that immunotherapy suppressed elimination. Our findings indicate pathogenic could be one leading causes comprehensive triggered by Thus, can propose an efficient therapeutic target fight devastating disorder.