CSPα knockout causes neurodegeneration by impairing SNAP‐25 function

摘要: At a synapse, the synaptic vesicle protein cysteine-string protein-α (CSPα) functions as co-chaperone for SNARE SNAP-25. Knockout (KO) of CSPα causes fulminant neurodegeneration that is rescued by α-synuclein overexpression. The KO decreases SNAP-25 levels and impairs SNARE-complex assembly; only latter but not former reversed α-synuclein. Thus, question arises whether phenotype due to decreased function then neurodegeneration, or dysfunction multiple as-yet uncharacterized targets. Here, we demonstrate decreasing in mice either knockdown aggravated their phenotype. Conversely, increasing overexpression Inactive mutants were unable rescue, showing rescue was specific. Under all conditions, neurodegenerative precisely correlated with assembly, indicating impaired assembly ultimate correlate neurodegeneration. Our findings suggest primarily produced defective function, which impairing assembly.