title: Dual leucine zipper kinase as a therapeutic target for neurodegenerative conditions.
abstract: Dual leucine zipper kinase (DLK) is a serine/threonine protein kinase that is a member of the mixed lineage kinase subfamily. Mixed lineage kinases are upstream MAP3Ks that activate the JNK pathway. DLK is primarily responsible for activating JNK and mediating the apoptotic stress response in various cell types, specifically neurons. Inhibition and knockdown of DLK has been demonstrated to have neuroprotective effects in cellular and animal models of Alzheimer's disease, glaucoma, Parkinson's disease and other neurodegenerative conditions. Several series of ATP-binding site inhibitors have been identified through profiling efforts providing launch points for future medicinal chemistry programs.
authors.affiliation: John Hopkins University Brain Science Institute, 855 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Ferraris
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.forename: Derek
authors.initials: D
authors.lastname: Welsbie
mesh_terms: D000818:Animals; D006801:Humans; D007191:Indazoles / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016350:Leucine Zippers; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12