This is illustrated by the existence of hereditary neurodegenerative diseases in which affected individuals harbour mutations in tyrosyl DNA phosphodiesterase 1 (TDP1) or tyrosyl DNA phosphodiesterase 2 (TDP2) (32,33), DNA repair proteins with activities dedicated to removing trapped topoisomerases from DNA breaks (32, 33, 34). This evidence concerns the gene TDP1 and neurodegenerative disease.