The mechanism for MMP-9 neurotoxicity in ALS may be due to upregulating neuronal TNF-α (tumor necrosis factor alfa) expression and activation; MMP-9 was involved in cleavage of TNF-α from its membrane-bound form via its receptor (TNF-R1), leading to cells’ apoptosis. This evidence concerns the gene MMP9 and amyotrophic lateral sclerosis.