Fig. 7

Schematic representation of the effect of PTP1B inhibition on the neurotoxicity of glial TDP-43 overexpression. In the disease state, an increase in cytoplasmic TDP-43 aggregation in astrocytes leads to the accumulation of PTP1B. PTP1B upregulation activates NF-κB p65 and induces the translocation of NF-κB to the nucleus. Nuclear NF-κB upregulates the transcriptional level of proinflammatory genes. This transcriptional activation increases the secretion of proinflammatory cytokines and chemokines, such as IL-1β, IL-6 and TNF-α. Subsequently, the extensive secretion of proinflammatory cytokines and chemokines leads to neuronal death. Thus, PTP1B inhibition mitigates neurodegeneration caused by TDP-43-induced inflammation in astrocytes