It seems that endocytosis is the most important factor for expansion of a-syn in brain tissue. Additionally, it seems that knock-out mice have no problem in their essential functions of the brain, so we can conclude that endocytosis is doing properly in their brain. Therefore, I think, it is interesting to know what other factors can be involved in the expansion process that are affected by the absence of endogenous a-syn? Is there any other hypothesis in this manner?
Article α-Synuclein: The Long Distance Runner
One issue could be the difference in the inflammatory response. We have a emerging body of literature on that point. Essentially, the Snca KO mouse is in a state in which the microglia are already to some degree in an activated state, in vivo and in culture. This very well may alter the impact of fibril injection on pathology. Although your definition of pathology is a bit vague as well as what fibrils you are injecting.
I assume your question is in the context of the intracerebral injection of alpha-synuclein fibrils. Some of those experiments (cited in George et al 2013) are meant to investigate the hypothesis that a misfolded form of alpha-synuclein (here the fibrils) can transmit its pathological conformation to normal alpha-synuclein (when injected into the brain), and induce a spread of synucleinopathy throughout the brain. In those experiments, SNCA KO mice are used as " controls", and it was shown that when no endogenous alpha-synuclein is present in the brain (SNCA KO mice), asyn fibrils cannot induce a spread of pathology (Luk et al. 2012, Science- see suppl. figure S6). Now regarding inflammation, the intracerebral injection by itself induces also an inflammatory response, so i think both WT mice, and SNCA mice are in a comparable state of inflammation, and this does not alter their response to fibrils injection in one mouse line or the other.
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