Dual leucine zipper kinase as a therapeutic target for neurodegenerative conditions.

Dana Ferraris; Zhiyong Yang; Derek Welsbie

doi:10.4155/fmc.13.150

Dual leucine zipper kinase as a therapeutic target for neurodegenerative conditions.

Dana Ferraris, Zhiyong Yang, Derek Welsbie

Research output: Contribution to journal › Review article › peer-review

19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1923-1934
Number of pages	12
Journal	Future medicinal chemistry
Volume	5
Issue number	16
DOIs	https://doi.org/10.4155/fmc.13.150
State	Published - Oct 2013
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Pharmacology
Drug Discovery

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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.",

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AB - 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.

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Dual leucine zipper kinase as a therapeutic target for neurodegenerative conditions.

Abstract

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