TDP-43 in the spectrum of MND-FTLD pathologies

•TDP-43 is an RNA-binding protein implicated in neurodegeneration.•This review summarizes existing knowledge and new contributions to the TDP-43 field.•TDP-43 disruption leads to synaptic dysfunction and neurotransmitter balance.

The relationship between RNA-binding proteins, particularly TAR DNA binding protein 43 (TDP-43), and neurodegeneration is an important area of research. TDP-43 is involved in so many cellular processes that perturbation of protein homeostasis can lead to countless downstream effects. Understanding what leads to this disease-related protein imbalance and the resulting cellular and molecular effects will help to develop targets for disease intervention, whether it be prevention of protein accumulation, or addressing a secondary effect of protein accumulation. Here we review the current literature of TDP-43 and TDP-43 pathologies, the effects of TDP-43 overexpression and disruption of synaptic proteins through its binding of messenger RNA, leading to synaptic dysfunction. This review highlights some of the still-limited knowledge of the protein TDP-43 and how it can contribute to disease.