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. 2020 Nov 17;8:598446. doi: 10.3389/fcell.2020.598446

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Copyright © 2020 Wildburger, Hartke, Schidlitzki and Richter.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Reciprocal feedback loop of GCase inhibition and aSyn accumulation. CtsD functionality depends on GCase activity. When GCase activity is diminished, the lysosomal enzyme CtsD, which plays a role in aSyn degradation becomes limited. This leads to the accumulation of aSyn in cells. Likewise, elevated levels of aSyn (via multiple mechanisms) inhibits GCase to either initiate or enhance the destructive positive feedback loop of lysosomal impairment and aSyn accumulation (see text for details).