Faster cell breakdown in vulnerable motor neurons increases when TDP-43 is lost in a zebrafish model of ALS

ALS-vulnerable large spinal motor neurons showed unusually high degradation activity that increased further with TDP-43 loss in zebrafish.

This zebrafish model study monitored autophagy at single-cell resolution across spinal and ocular motor neurons and assessed autophagy, proteasome-mediated degradation, unfolded protein response pathways, and axon outgrowth after degradation inhibition.

The mechanism is inferred from a zebrafish TDP-43 loss model and cell-size comparisons, so its relevance to human ALS progression and therapy remains uncertain.