In summary, we showed that proteasome inhibition by MG-132 in primary neurons and the NSC-34 motor neuron cell line is sufficient to induce cytoplasmic accumulation, aggregation, fragmentation and insolubility of TDP-43, bearing similarities to the TDP-43 pathology in FTLD-TDP and ALS. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.