Fig. 1

A model of how metabolic processes might contribute to abnormal TDP-43 aggregation in ALS/FTD. TDP-43 is primarily a nuclear protein that mislocalizes to the cytoplasm of neurons in pathological conditions, such as ALS/ FTD, where it undergoes phosphorylation and ubiquitination and forms cytoplasmic aggregates. Glucose starvation might contribute to the formation of TDP-43 aggregates by inducing the formation of stress granules. These stress granules might serve as precursors to TDP-43 inclusions. Similarly, caloric restriction might contribute to TDP-43 aggregation by triggering auto-phagosomes formation, which might serve as another site for TDP-43 aggregation