Targeting the JNK signaling pathway for stroke and Parkinson's diseases therapy.
The c-Jun NH2-terminal Kinase (JNK) signaling pathway is frequently induced by cellular stress and correlated with neuronal death. This unique property makes JNK signaling a promising target for developing pharmacological intervention. Among several neurological disorders, JNK signaling is particularly implicated in ischemic stroke and Parkinson's disease. The inhibitors of the JNK signaling pathway include upstream kinase inhibitors (for example, CEP-1347), small chemical inhibitors of JNK (SP600125 and AS601245), and peptide inhibitors of the interaction between JNK and its substrates (D-JNKI and I-JIP). The mechanisms by which JNK signaling induces apoptosis and evidence of cytoprotective effects of these JNK inhibitors are summarized in the present review.
Kuan
Chia-Yi
CY
Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA. alex.kuan@chmcc.org
Burke
Robert E
RE
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020521:Stroke / Q000188:drug therapy / Q000201:enzymology*
D004791:Enzyme Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases