Over the past two decades, c-Jun N-terminal Kinase (JNK) signaling has received considerable attention and becomes a therapeutic target for a number of diseases, namely, neurological, coronary, hepatobiliary, and respiratory diseases; and autoimmune, inflammatory, and cancer conditions.
JNKs are a family of protein kinases that play a central role in stress signaling pathways implicated in gene expression, neuronal plasticity, regeneration, cell death, and regulation of cellular senescence. According to relevant researchers, JNK pathway would be possibly activated when exposed to a series of stressing factors, such as cytokines, growth factors, unfolded protein response signals, Aβ peptides and more.
Generally speaking, JNKs have become a focus of screening strategies aiming for new therapeutic approaches to common diseases like diabetes or cancer. What’s more, activation of JNK has been viewed by experts as a key element responsible for regulating apoptosis signals. As a result, JNK inhibitors are quite critical for pathological cell death resulting from neurodegenerative diseases, Alzheimer’s disease (AD) representatively. Besides, findings from in vitro and in vivo studies have reported likely association between alterations of JNK pathways with pathogenesis and neuronal death in AD. Researches have proved the importance of JNKs in neurodegenerative diseases. To cite an example here, JNK3 helps in not only enhancing Aβ production, but also accelerating the maturation and development of neurofibrillary tangles.
Over the past decade, scientists have unveiled many signaling pathways. Nowadays, we know in great detail about how a specific signal is transmitted via specific signaling pathways, from the membrane to the nucleus, to change the functions of a cell. Coordinated interaction of the scaffold proteins belonging to the JNK activation complex are needed to activate the JNK pathway. These scaffold proteins are powerful in not only mediating the biochemical signal amplification but also guaranteeing substrate-specificity as well as a coordinated cascade signaling.