TDP-43 inclusions do not protect motor neurons from sporadic ALS

Excerpt

Patients with SALS and non-SOD1 mutant familial ALS (FALS) have cytoplasmic aggregates of TAR DNA binding protein 43 (TDP-43) in motor neurons and glia (Tan et al., Acta Neuropathol 113: 535, 2007). This suggests that TDP-43 has a central role in the pathogenesis of ALS. Reports of mutations in the gene encoding TDP-43, TARDBP, in patients with either FALS or SALS (Sreedharan et al., Science 319: 1668, 2008) strengthens the possibility that TDP-43 is primarily implicated in ALS. The relationship of TDP-43 inclusions with neuronal death in ALS is, however, unknown. It remains possible that TDP-43 inclusions are by-products of the pathological process in the majority of ALS patients who do not have TARDBP mutations. TDP-43 inclusions could in fact protect motor neurons from damage, as has been suggested for other protein aggregates in neurodegenerative diseases (Ross et al., Nat Rev Mol Cell Biol 6: 891, 2005). …