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In ALS, there is an abnormal cytoplasmic aggregation of misfolded proteins, mainly DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS) (Wijesekera and Leigh 2009)

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Since kidney function is reduced during AKI, activation of the urea cycle and subsequent urea generation together lead to a substantial rise in BUN 14,35

Together these observations are consistent with an important concept: microglia are the earliest responders to a primary multifocal myelin injury in the MS white matter, and importantly, this injury/response seems to precede lymphocytic infiltration, arguing against adaptive immune cells being the primary drivers of white matter injury