Recent studies have identified mutations in the genes encoding TDP-43 and FUS/TLS in patients with
amyotrophic lateral sclerosis (ALS). Both TDP-43 and FUS/TLS display all the characteristics of a
heterogeneous nuclear ribonucleoprotein, which regulates various aspects of RNA processing. In addition, TDP-43 is partly cleared from the nuclei of neurons containing cytoplasmic aggregates, suggesting loss of normal TDP-43 function in the nucleus, leading to defects or alterations in
RNA metabolism, plays, at least in part, a causative role in the pathogenesis of ALS. TDP-43 has been reported to be involved in the Drosha complex required for the biogenesis of
microRNAs. The high expression level of
microRNAs and the exclusive expression of certain
microRNAs in the central nervous system highlights their
biological importance at all stages of neural development as well as in differentiated neurons. In addition, the altered expression of certain
microRNAs has been implicated in the pathogenesis of
neurodegenerative diseases. Therefore, elucidation of the role of TDP-43 in
microRNA biogenesis as a component of the Drosha complex is indispensable to understanding pathophysiology of ALS. In addition, the identification of TDP-43-regulated
microRNAs associated with motor neuron death is expected to further contribute to the development of novel therapeutic strategies for ALS treatment.