CASP3 and amyotrophic lateral sclerosis: Prior to the discovery of TDP-43 as the primary component of insoluble inclusions in ALS and FTLD (Neumann et al., 2006), elevated caspase-3 activity had been noted in the anterior horn and motor cortex of ALS patients (Martin, 1999), as well as in degenerating astrocytes and neurons exhibiting DNA damage in the superior frontal gyrus and anterior pole of the temporal lobe of the FTLD brain (Su et al., 2000).