I think this is a great paper that unravels a novel role for VAMP/synaptobrevin-associated protein B (VAPB) with great precision. The paper again illustrates the power of Drosophila
and C. elegans
as animal models for identifying functional roles of proteins and illuminating potential disease pathways.
The questions raised by the P56S-VAPB mutation are essentially the same as those raised by mutations in genes linked to other ALS forms, as well as to other neurodegenerative disorders: What is the function of the mutated protein? Does the disease result from a loss of its normal function or a gain of toxic activity? What is the role of protein aggregation? What determines the delayed onset of disease, and to what extent do disease pathways overlap with those in other ALS forms? And, most importantly, how to stop or prevent disease?
Several lines of evidence indicate that mutant VAPB, at least in part, may operate in a dominant-negative way by recruiting wild-type VAPB to inclusions. the paper by Han et al. provides one potential mechanism by which loss of...