Fig. 5

Abstract picture. Under normal conditions, GCase is synthesized in the endoplasmic reticulum (ER)-bound polysomes, from which it is transferred to the ER. After glycosylation, GCase is transported to the Golgi apparatus and then to the lysosome, and α-synuclein is normally degraded. Under abnormal conditions, the mutation of the rs12411216 site leads to a decrease in e2f4 binding efficiency, which will cause a reduction or loss of GCase activity. GCase cannot be transported to the lysosome, causing the accumulation and oligomerization of α-synuclein and eventually the formation of a Lewy body. In turn, elevated α-synuclein inhibits lysosomal maturation and the activity of normal GCase. α-Synuclein prevents the transfer of GCase from the endoplasmic reticulum to the lysosomes