Fig. 1.

A: Cellular membrane trafficking encompasses 4 major types: (1) secretory or exocytic route, (2) endocytic pathway; (3) newly synthesized biomolecules delivery; and (4) autophagy pathway (Fig. 1A). ER = endoplasmic reticulum. V = transport vesicle. LE = late endosome. EE = early endosome. EL = endolysosome. AP = autophagosome. L = lysosome. B: Example of LE and lysosomal membrane fusion in the inset of A. Membrane fusion is mediated by active SNAREs tethering to bring two membranes together. After membrane fusion, SNAREs form inactive complexes and must be regenerated by NSF ATPase for the next round of fusion. During this process, NSF ATPase binds to inactive SNAREs via a SNAP adaptor to hydrolyze adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and inorganic phosphate for providing the energy. Brain ischemia leads to deposition NSF into inactive protein aggregates, thus stopping all membrane trafficking activities in postischemic neurons.