TABLE 2.

Summary of ALS Disease Pathophysiology in Humans, Mice, and Zebrafish

	Neuronal stress	Electro physiology	NMJ denervation	Cellular changes, insoluble aggregates	Astrocytosis/ Microgliosis/ Mitochondria/ Inclusion/UPS	Gross motor symptoms
Human	?	Prior to onset in adults†	Prior to onset in adults†	Golgi, mitochondria, insoluble aggregates In post-mortem specimens	In post-mortem specimens	40-50 years
Mouse (Sod1G93 AHiGur)	?	12 dpf* to 6 dpp** (G85R, G93Alow)	∼30dpp	Golgi changes ∼40-50dpp	∼70-90dpp	∼100dpp
Zebrafish (G93R)	24 hpf ** (This manuscript)	96hpf** (This manuscript)	Normal NMJ but reduced staining at 11dpf. 6 months and 1 year Observed denervation in stressed motor neuron (This manuscript)	UPR at 1 month***.	No gross inflammation (unpublished) Motor neuron stress. 6-months (This manuscript)	1 year

dpf: days post fertilization; hpf: hours post fertilization; dpp: days postpartum. UPR: Unfolded Protein Response †earliest tested, * earliest tested in organotypic culture; ** Earliest tested in intact spinal cord, *** Personal communication (C.Beattie)