biostudies-literatureRousseaux MWCNICHD NIH HHSNINDS NIH HHSCIHR9286-9301https://www.ebi.ac.uk/biostudies/studies/S-EPMC6199406biostudies-literatureUnknown38(43)Accumulation of α-Synuclein (α-Syn) causes Parkinson's disease (PD) as well as other synucleopathies. α-Syn is the major component of Lewy bodies and Lewy neurites, the proteinaceous aggregates that are a hallmark of sporadic PD. In familial forms of PD, mutations or copy number variations in <i>SNCA</i> (the α-Syn gene) result in a net increase of its protein levels. Furthermore, common risk variants tied to PD are associated with small increases of <i>wild-type</i> α-Syn levels. These findings are further bolstered by animal studies which show that overexpression of α-Syn is sufficient to cause PD-like features. Thus, increased α-Syn levels are intrinsically tied to PD pathogenesis and underscore the importance of identifying the factors that regulate its levels. In this study, we establThe Journal of neuroscience : the official journal of the Society for NeuroscienceA Druggable Genome Screen Identifies Modifiers of α-Synuclein Levels via a Tiered Cross-Species Validation Approach.PMC6199406R21 NS096395U54 HD083092R21 NS089854Jeong HHKim JJShulman JMXu QElledge SJRevelli JPWestbrook TFBajic ALi MZKang HLiu ZLavery LAZoghbi HYRousseaux MWCKim JYAl-Ramahi IBotas JPhan ETPerez AMVazquez-Velez GEDeger JMYe HfalseA Druggable Genome Screen Identifies Modifiers of α-Synuclein Levels via a Tiered Cross-Species Validation Approach.Accumulation of α-Synuclein (α-Syn) causes Parkinson's disease (PD) as well as other synucleopathies. α-Syn is the major component of Lewy bodies and Lewy neurites, the proteinaceous aggregates that are a hallmark of sporadic PD. In familial forms of PD, mutations or copy number variations in <i>SNCA</i> (the α-Syn gene) result in a net increase of its protein levels. Furthermore, common risk variants tied to PD are associated with small increases of <i>wild-type</i> α-Syn levels. These findings are further bolstered by animal studies which show that overexpression of α-Syn is sufficient to cause PD-like features. Thus, increased α-Syn levels are intrinsically tied to PD pathogenesis and underscore the importance of identifying the factors that regulate its levels. In this study, we establ2018-01-01T00:00:00Z2018 Oct2026-04-07T15:23:01.63Z2019-06-06T22:45:52ZS-EPMC61994063024979210.1523/JNEUROSCI.0254-18.201810.1523/jneurosci.0254-18.2018