JNK: a stress-activated protein kinase therapeutic strategies and involvement in Alzheimer's and various neurodegenerative abnormalities.
The c-Jun N-terminal kinase (JNKs), also known as stress-activated protein kinase (SAPK), is one such family of multifunctional-signaling molecules, activated in response to wide range of cellular stresses as well as in response to inflammatory mediators. JNKs regulate various processes such as brain development, repair, and memory formation; but on the other hand, JNKs are potent effectors of neuroinflammation and neuronal death. A large body of evidence indicates that JNK activity is critical for normal immune and inflammatory response. Indeed, aberrant activation of JNK has been implicated in the pathogenesis of Alzheimer's disease. Moreover, the JNK pathway is considered to be a key regulator of various inflammatory pathways which are activated during normal aging and Alzheimer's disease therapy as well as key regulator of pro-inflammatory cytokines biosynthesis at the transcriptional and translational levels, which makes different components of these pathway potential targets for the treatment of autoimmune and inflammatory diseases. Pharmacological inhibition of JNK has been demonstrated to attenuate microglial activation and the release of neurotoxic chemicals including pro-inflammatory cytokines. In this review, we provide an overview on implications and therapeutic strategies of JNK in neurodegenerative disorders.
Mehan
Sidharth
S
Department of Pharmacology, GD Memorial College of Pharmacy, Jodhpur, 342005, Rajasthan, India. sidh.mehan@gmail.com
Meena
Harikesh
H
Sharma
Deepak
D
Sankhla
Rameshwar
R
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008958:Models, Molecular; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D011487:Protein Conformation
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D048031:JNK Mitogen-Activated Protein Kinases