A new model to study cell-to-cell transfer of αSynuclein in vivo

Biochemical and Biophysical Research Communications
Gabriela MercadoClaudio Hetz

Abstract

Parkinson's disease (PD) compromises motor control due to the loss of dopaminergic neurons in the substantia nigra pars compacta. At the histopathological level, PD is characterized by the accumulation of Lewy bodies, large protein inclusions containing aggregated αSynuclein (αSyn). The progression of PD involves the spreading of αSyn misfolding through the brain mediated by a prion-like mechanism, where the protein is transferred between cells. Here we report that αSyn internalization is a dynamic process, where the protein transits through different sub-cellular compartments. Importantly, cells incorporating αSyn develop larger protein-like inclusions when compared to αSyn producing cells. We developed a new tool to monitor cell-to-cell transfer of αSyn in vivo using an adeno-associated viral (AAV) vector expressing αSyn fused to a red fluorescent protein in addition to soluble EGFP to label donor cells. Intra-nigral delivery of this reporter AAV construct allowed the visualization of αSyn incorporation into surrounding neurons. This work provides a new tool to study αSyn cell-to-cell transfer in vivo and may open new opportunities to study PD pathogenesis.

Citations

Nov 17, 2019·International Journal of Molecular Sciences·Kai-Jung LinTsu-Kung Lin
Feb 6, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·René L VidalClaudio Hetz
Apr 28, 2021·Proceedings of the National Academy of Sciences of the United States of America·Xue YangJean Baum

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