The paper noted here is an illustrative snapshot of one tiny part of the search for new mechanisms of action that takes place constantly in academia and the pharmaceutical industry. Cell metabolism remains an only partially charted expanse, the high points filled in, and mostly a blank canvas in between. The poorly explored regions of metabolism could yield any number of interesting points of intervention, each a starting point for the present industry-standard approach of small molecule drug discovery. That said, there isn't that much of an incentive to pour funds into search initiatives because the odds of success in the current paradigm are very low. The vast majority of discoveries do not lead to even marginally useful drugs. Hence there is considerable interest at the present time in the development of new computational infrastructure technologies that can reduce the cost of discovery in some way.
Traf2- and Nck-interacting kinase (TNIK) has emerged as a key regulator of pathological metabolic signaling in several diseases and is a promising drug target. Originally studied for its role in cell migration and proliferation, TNIK possesses several newly identified functions that drive the pathogenesis of multiple diseases. Specifically, we evaluate TNIK's newfound roles in cancer, metabolic disorders, and neuronal function. We emphasize the implications of TNIK signaling in metabolic signaling and evaluate the translational potential of these discoveries. TNIK signaling appears to converge on four critical hallmarks of aging: cellular senescence, deregulated nutrient sensing, chronic inflammation, and altered intercellular communication. TNIK's contribution to these processes implicate it as a possible contributor to aging-related pathology, particularly by promoting conditions like cancer and metabolic dysregulation. Thus, as aging has been revealed to increase the incidence and severity of the aforementioned diseases in this opinion article, an interesting hypothesis would be whether TNIK dysregulation contributes to the aging process itself or is a consequence of it.
Link: https://doi.org/10.1016/j.tips.2024.04.010
