Fig. 1

Golgi defects accelerate SARS-CoV-2 virus maturation in COVID-19 and Aβ production in AD. (A) In healthy cells, Golgi structure formation serves as a quality control mechanism for protein glycosylation and sorting. When Golgi cisternae are fully stacked, which is mediated by Golgi structural proteins including GRASP55 and GRASP65, vesicles can only form and fuse at the rims. This slows down trafficking, but enforces accurate glycosylation and sorting [4]. (B) In COVID-19, SARS-CoV-2 infection causes Golgi fragmentation possibly by downregulating GRASP55 expression, which may accelerate virus maturation and release. (C) In AD, Aβ oligomer accumulation leads to the influx of Ca²⁺ ions; increased cytosolic Ca²⁺ activates calpain to cleave p35 to p25. p25 then activates cdk5 for GRASP65 phosphorylation. GRASP65 phosphorylation results in Golgi fragmentation, which, in turn, accelerates APP trafficking and increases Aβ production [9]. In addition, Golgi defects also cause autophagy and lysosomal dysfunction [4] and impact the synthesis of glycolipids [4, 7], major components of the myelin sheath.