Figure 8.

Hypothetical model of causes and effects of TMEM106B overexpression in FTLD-TDP. Our data are compatible with a model whereby decreased levels of miR-132/212 result in increased TMEM106B expression. As a result, increased TMEM106B expression leads to (1) endosomal–lysosomal dysfunction, which may in turn further increase levels of TMEM106B, and also to (2) perturbation of progranulin pathways, thereby increasing the risk of developing FTLD-TDP. Black arrows indicate steps evidenced by the current study, gray arrows indicate steps reported in the literature, and yellow arrows indicate hypothetical steps.