What is it about?

38 genes regulate the cell-to-cell transfer of α-synuclein and they might be relevant for Parkinson. We undertook a small interfering RNA (siRNA), genome-wide screen to identify genes regulating the cell-to-cell transfer of α-synuclein. A genetically encoded reporter, GFP-2A-αSynuclein-RFP, suitable for separating donor and recipient cells, was transiently transfected into HEK cells stably overexpressing α-synuclein. We find that 38 genes regulate the transfer of α-synuclein-RFP, one of which is ITGA8, a candidate gene identified through a recent PD genome-wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) show that those hits cluster in networks that include known PD genes more frequently than expected by random chance. The findings expand our understanding of the mechanism of α-synuclein spread.

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Why is it important?

Those found 38 genes can lead to new ideas for treatments

Perspectives

Neuropathological and experimental evidence suggests that the cell-to-cell transfer of α-synuclein has an important role in the pathogenesis of Parkinson’s disease (PD).

Alessandro Crimi
Universitat Zurich

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This page is a summary of: An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of α-synuclein, Cell Reports, June 2021, Elsevier, DOI: 10.1016/j.celrep.2021.109189.
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