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

<p>Abstract</p> <p>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...

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Main Authors: Van Eldik Linda J, de Almeida Lucia, Borders Aaron S, Watterson D Martin
Format: Article
Language:English
Published: BMC 2008-12-01
Series:BMC Neuroscience
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author Van Eldik Linda J
de Almeida Lucia
Borders Aaron S
Watterson D Martin
author_facet Van Eldik Linda J
de Almeida Lucia
Borders Aaron S
Watterson D Martin
author_sort Van Eldik Linda J
collection DOAJ
description <p>Abstract</p> <p>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.</p>
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spelling doaj.art-e97da5ba6d9d413dbb00cbb7f55a9ca42022-12-22T03:29:04ZengBMCBMC Neuroscience1471-22022008-12-019Suppl 2S1210.1186/1471-2202-9-S2-S12The p38α mitogen-activated protein kinase as a central nervous system drug discovery targetVan Eldik Linda Jde Almeida LuciaBorders Aaron SWatterson D Martin<p>Abstract</p> <p>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.</p>
spellingShingle Van Eldik Linda J
de Almeida Lucia
Borders Aaron S
Watterson D Martin
The p38α mitogen-activated protein kinase as a central nervous system drug discovery target
BMC Neuroscience
title The p38α mitogen-activated protein kinase as a central nervous system drug discovery target
title_full The p38α mitogen-activated protein kinase as a central nervous system drug discovery target
title_fullStr The p38α mitogen-activated protein kinase as a central nervous system drug discovery target
title_full_unstemmed The p38α mitogen-activated protein kinase as a central nervous system drug discovery target
title_short The p38α mitogen-activated protein kinase as a central nervous system drug discovery target
title_sort p38α mitogen activated protein kinase as a central nervous system drug discovery target
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