TDP-43: a DNA and RNA binding protein with roles in neurodegenerative diseases

Transactive response DNA binding protein 43 kDa (TDP-43) is a DNA and RNA binding protein involved in RNA processing and with structural resemblance to heterogeneous ribonucleoproteins (hnRNPs). TDP-43 serves multiple functions with roles in transcriptional regulation, pre-mRNA splicing and translational regulation. TDP-43 is also crucial for embryonic development with increasing evidence indirectly implicating its involvement in other cellular processes including microRNA biogenesis, apoptosis and cell division. The role of TDP-43 in neurodegeneration has been actively studied since identification as a major component of the ubiquitinated inclusions seen in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TDP-43 pathology has also been identified in several other neurodegenerative diseases. These disorders are collectively referred to as TDP-43 proteinopathies. The identification of rare TDP-43 mutations in sporadic and familial forms of ALS and FTLD suggests TDP-43 plays an important pathogenic role, rather than merely being a marker of the disease.