A Feedforward Loop Links Gaucher and Parkinson's Diseases? Mark R. Cookson  Cell  Volume 146, Issue 1, Pages 9-11 (July 2011) DOI: 10.1016/j.cell.2011.06.031 Copyright © 2011 Elsevier Inc. Terms and Conditions

Figure 1 A Possible Mechanism Linking Parkinson's Disease to Gaucher Disease (A) Under normal conditions, α-synuclein is imported into the lysosome for degradation. The degradative enzyme glucocerebrosidase (GCase) is also imported into the lysosome after the enzyme matures through the ER-Golgi pathway. In pathogenic situations, accumulation of α-synuclein may block ER-Golgi transport, leading to the loss of GCase in the lysosome. This amplifies the effects by limiting degradation of α-synuclein, causing further accumulation of the protein and possibly other detrimental effects on the lysosome. (B) If this series of positive feedback loops (small circles with arrows) continues over time, then α-synuclein levels will tend to increase with age. Presumably, at a certain point, α-synuclein levels will exceed a pathogenic threshold (arbitrarily indicated by a red line) and be associated with disease. Cell 2011 146, 9-11DOI: (10.1016/j.cell.2011.06.031) Copyright © 2011 Elsevier Inc. Terms and Conditions