TDP-43 in neurodegenerative disorders

The number of neurodegenerative diseases associated with pathological aggregates of transactivation response element (TAR)-DNA-binding protein 43 (TDP-43) has increased, leading to the new designation 'TDP-43 proteinopathy.' Biochemically, TDP-43 proteinopathies are characterized by decreased solubility, hyperphosphorylation, and cleavage of TDP-43 into 25- and 35-kDa fragments, and by altered cellular localization.

This review summarizes research characterizing the distribution of TDP-43 pathology in human postmortem brain tissue and discusses possible therapeutic strategies based on genetic and in vitro studies.

We reviewed recent studies of TDP-43 proteinopathy.

Given that several different mutations can lead to TDP-43 proteinopathies, including mutations in progranulin and valosin-containing protein, research is needed to decipher and potentially exploit the link between these mutations and TDP-43 pathology.