Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.15.039578v1?rss=1 Authors: Peinado, J. R., Chaplot, K., Jarvela, T. S., Barbieri, E., Shorter, J., Lindberg, I. Abstract: Chaperone proteins perform vital functions in the maintenance of cellular proteostasis and play important roles during the development of neurodegenerative diseases involving protein aggregation. We have previously reported that a secreted neuronal chaperone known as proSAAS exhibits potent chaperone activity in vitro against protein aggregation and blocks the cytotoxic effects of amyloid and -synuclein oligomers. Here we report that overexpression of proSAAS generates dense, membraneless 2 m spheres which can increase by fusion up to 4 M during expression within the cytoplasm. The presence of dense proSAAS spheres was confirmed using electron microscopy. ProSAAS spheres selectively sequestered GFP-TDP-43216-414 within their cores, resulting in cellular redistribution and retardation of degradation. ProSAAS expression was protective against TDP-43 cytotoxicity in a yeast model system. Aggregate sequestration via proSAAS encapsulation may provide protection from cell-to-cell transmission of aggregates and explain the as-yet unclear mechanism underlying the cytoprotective chaperone action of proSAAS. Copy rights belong to original authors. Visit the link for more info