Hence, we tested this in our endogenous ALS-Tdp-43ΔNLS mouse model, and were the first to demonstrate in the brain (cortex and hippocampus) and spinal cord that nuclear clearance and subsequent pathological aggregation of Tdp-43 in MN-specific manner led to accumulation of DNA break foci, hyperactivation of neuroinflammatory factors such as Iba-1, Il-6, and Tnf-α, resulting in neuronal death. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.