This leads to upregulation of the Bcl-2 protein, change of autophagy, mis-metabolism of TDP-43 and other proteins, ER stress, etc., all of which would contribute to the age-dependent cytotoxicity/ death of the spinal cord MN and other age-dependent ALS-like phenotypes TDP-43 (N390D/+) mice. Here, TARDBP is linked to amyotrophic lateral sclerosis.