ATP regulates cytosolic viscosity in axons findings

Top left shows how the in vitro aggregation of the protein TDP-43 (associated with ALS), seen as white blobs, is dependent on the concentration of ATP (measured in millimolar, mM). The same is shown in vivo, where ALS neurons treated with NMN, which boosts ATP production, have fewer TDP-43 aggregations. Top right shows the correlation between ATP concentration, axoplasmic viscosity and TDP-43 aggregation in neurons.

Bottom left shows the cytosolic viscosity of untreated ALS neurons (“CTRL”) and neurons treated with NMN. The intensity of the color indicates the concentration of fluorescent molecules. These permanently lose their fluorescence when subjected to photobleaching via laser on the circled areas. If the cytoplasm is highly viscous, the molecules cannot move easily, resulting in less fluorescence recovery post-bleaching in untreated neurons compared to NMN-treated neurons. Bottom right shows quantification of axoplasmic viscosity (mobile fraction) and intracellular levels of ATP in ALS neurons with or without NMN treatment.