TDP-43: A KEY THERAPEUTIC TARGET BEYOND AMYOTROPHIC LATERAL SCLEROSIS.

Accumulation of TDP-43 in the cytoplasm of diseased neurons is the pathological hallmark of Frontotemporal Dementia-TDP (FTLD-TDP) and Amyotrophic Lateral Sclerosis (ALS), two diseases that lack of efficacious medicine to prevent or to stop disease progression. The discovery that mutations in the TARDBP gene (coding for the nuclear protein known as TDP-43) in both FTLD and ALS patients provided evidence for a link between TDP-43 alterations and neurodegeneration. The knowledge of TDP-43 function has advanced profoundly in the last years, however its complete role and the molecular mechanisms that lead to disease have yet to be fully understood. Here we summarize the recent studies of this protein, its relation to neurodegenerative diseases and the therapeutic strategies to restore its homeostasis with small molecules. Finally, we briefly discuss the available cellular and animal models that help to shed light on TDP-43 pathology and could serve as tools to discover pharmacological agents for the treatment of TDP-43 related diseases.