N-ethylmaleimide-sensitive factor (NSF)

N-ethylmaleimide-sensitive factor (NSF) is a highly conserved, homohexameric ATPase of the AAA+ (ATPases Associated with diverse cellular Activities) protein family, crucial for nearly all intracellular membrane trafficking events[1][3][5][7]. NSF acts by binding to and disassembling SNARE (soluble NSF attachment protein receptor) complexes after vesicle and target membrane fusion, a process key for recycling SNARE components and maintaining membrane trafficking throughout the cell[1][3][5][6][7]. NSF uses ATP hydrolysis to generate the mechanical force necessary for SNARE complex disassembly. Functional deficiency or mutation of NSF impairs vesicle fusion events and is implicated in several diseases, especially affecting neuronal function, given its essential role in neurotransmitter release and synaptic plasticity[5][7]. There are currently no drugs in clinical use specifically targeting NSF, primarily due to the protein’s ubiquitous and essential cellular roles, making it a challenging and risky therapeutic target.

Other names

N-ethylmaleimide sensitive fusion proteinNEM-sensitive factorNSF protein

Inhibition of ATPase activity blocks SNARE complex disassembly and vesicle trafficking