[RNA processing TDP-43 protein has a main pathological role in FTLD and ALS]

TDP-43 is mainly a nuclear protein belonging to the heterogeneous ribonucleoproteins family. It plays a crucial role in the regulation of gene transcription and RNA processing. In 2006, TDP-43 was characterized as the main component of ubiquitin-positive inclusions observed in Frontotemporal Lobar Degeneration (FTLD) and Amyotrophic Lateral Sclerosis (ALS) cases. Since then, its central role in a number of neurodegenerative diseases was confirmed, originating the TDP-43 proteinopathies term. Pathological TDP-43 redistributes and accumulates in the cytoplasm forming toxic aggregates. Plethora of animal models recapitulating features typical for human TDP-43 proteinopathies has been generated. However, the mechanism involving TDP-43 and causing functional disturbances, like dementia and motoneurons degeneration, remains unknown. Loss and gain of function hypotheses are proposed, but they still need to be verified.