However, it seems likely that apoptosis is not initiated directly by inclusions themselves, but rather by some upstream process activated by a toxic species (perhaps mSOD1 oligomers), as has been suggested for ALS (using animal models, transgenic mice expressing mutant SOD1 [15], [16]) and other neurodegenerative diseases [reviewed in refs [15], [16], [17], [18]. Here, SOD1 is linked to amyotrophic lateral sclerosis.