Monday, October 1, 2018

Cross-species study to identify modifiers of alpha-synuclein levels

Rousseaux MWC, Vázquez-Vélez GE, Al-Ramahi I, Jeong HH, Bajic A, Revelli JP, Ye H, Phan ET, Deger JM, Perez AM, Kim JY, Lavery LA, Xu Q, Li MZ, Kang H, Kim JJ, Shulman JM, Westbrook TF, Elledge SJ, Liu Z, Botas J, Zoghbi HY. A druggable genome screen identifies modifiers of α-synuclein levels via a tiered cross-species validation approach. J Neurosci. 2018 Sep 24. pii: 0254-18. PMID: 30249792.

From the abstract: "Accumulation of α-Synuclein (α-Syn) causes Parkinson's disease (PD) as well as other synucleopathies. ... 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 establish a pooled RNAi screening approach and validation pipeline to probe the druggable genome for modifiers of α-Syn levels and identify 60 promising targets. Using a cross-species, tiered validation approach, we validate six strong candidates that modulate α-Syn levels and toxicity in cell lines, Drosophila, human neurons and mouse brain of both sexes. ... This approach has broad applicability to the multitude of neurological diseases that are caused by mutations in genes whose dosage is critical for brain function."

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