Amyotrophic lateral sclerosis (ALS)

The tumor suppressor protein p53 counts among the rare molecules known to regulate Bax expression. In normal situations, p53 basal levels in the cell are very low, but upon activation, as seen in pathological situations, there is a rapid rise in p53 mRNA and protein levels, as well as posttranslational modifications that stabilize the protein. Activation of the p53 pathway in ALS is evidenced by the demonstration that p53 is increased in the nuclear fraction of affected brain regions in ALS patients, as is p53 immunostaining in neuron nuclei of transgenic SOD1 G86R mice. Despite the compelling evidence that p53 is activated in ALS, two independent studies have failed to provide any supportive data for an actual role for this transcriptional factor in mutant SOD1–mediated neurodegeneration.