The p38α mitogen-activated protein kinase as a central nervous system drug discovery target

Aaron S. Borders, Lucia de Almeida, Linda J. Van Eldik, D. Martin Watterson

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/ threonine protein kinase, p38α mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38α MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38α MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38α MAPK in neurodegenerative disorders.

Original languageEnglish
Article numberS12
JournalBMC Neuroscience
Volume9
Issue numberSUPPL. 2
DOIs
StatePublished - Dec 3 2008

Bibliographical note

Funding Information:
This research was supported in part by a grant from the Alzheimer's Drug Discovery Foundation, and NIH grants AG031311 (DMW) and AG013939 (LVE). ASB is a postdoctoral trainee previously supported by NIH T32 AG000260 and currently supported by NIH F32 AG032842.

Funding Information:
wswuwpp.bleiommeentd>ce<nttirtalel.>co<mp/>cPornotceenet/dpidnfg/s14o7f 1th-2e280<2s-9u-pS>2t-hin<fo/s.pudpf><I/nutrel>rn<at/isounpapll eCmoennfet>rence on Alzheimer's Disease Drug Discovery</p> </title> <editor>Howard Fillit</editor> <sponsor> <note>The publication of this supplement was made possible by the generous support of the conference sponsors: Forest Laboratories, Inc.; Bellus Health Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; Esai, Inc., Ortho-McNeil Neurologics, Inc.; Sanofi-Aventis US, Inc.; Schering-Plough; Accera, Inc.; Acumen Pharmaceuticals, Inc.; Pfizer Inc.; and Wyeth Research.</note> </sponsor> <note>Reviews</note> <url>http://

ASJC Scopus subject areas

  • General Neuroscience
  • Cellular and Molecular Neuroscience

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