Mitogen-activated protein kinase 8 (MAPK8) (MAPK8)

Mitogen-activated protein kinase 8 (MAPK8), also known as c-Jun N-terminal kinase 1 (JNK1), is a serine/threonine kinase that integrates signals from environmental stresses, pro-inflammatory cytokines, and growth factors [1, 2]. Upon activation, MAPK8 phosphorylates the transcription factor c-Jun, thereby regulating the expression of genes involved in apoptosis, cell proliferation, and inflammatory responses [1, 3]. In metabolic health, MAPK8 is a critical mediator of obesity-induced insulin resistance, making it a prominent target for type 2 diabetes and non-alcoholic steatohepatitis (NASH) [4]. It is also implicated in the pathogenesis of fibrotic diseases and neurodegeneration, where its signaling promotes tissue scarring and neuronal cell death [5]. Therapeutic strategies targeting MAPK8 include small-molecule inhibitors that block its catalytic activity and antisense oligonucleotides (ASOs) designed to induce the degradation of MAPK8 mRNA [6]. However, clinical development has faced challenges such as hepatotoxicity and the need for high selectivity among JNK isoforms to avoid adverse systemic effects [5, 6].

Other names

JNK1c-Jun N-terminal kinase 1SAPK1PRKM8JNK-46

Inhibition of kinase activity through ATP-competitive binding or covalent modification; degradation of target mRNA via RNase H-mediated cleavage using antisense oligonucleotides.