Abstract
The signaling pathways which contribute to neuronal death during development, aging and disease have been extensively studied. While initial efforts focused on developmental death, increasing evidence suggests that mitogenactivated protein kinase pathways play a role in human pathology. In particular, the c-Jun N-terminal kinases (JNKs), mitogen- activated protein kinases activated by extracellular stimuli including stress, are a major focus. Knock-out mouse studies have demonstrated that removing particular JNK genes can reduce the severity in various disease scenarios, including those which are used to model Parkinsons disease and cerebral ischemia. In addition, activation of JNKs can be seen in human disease tissue. In this review we bring together the evidence for JNK being an important regulator of neuronal loss and outline the advancement of small molecule inhibitors for future therapeutic intervention.
Keywords: Mitogen-activated protein kinase, c-Jun N-terminal kinase, phosphorylation, neurodegeneration, Alzheimer's disease, Parkinson's disease, neuroprotection
CNS & Neurological Disorders - Drug Targets
Title: MAP Kinase Pathways in Neuronal Cell Death
Volume: 7 Issue: 1
Author(s): Karen L. Philpott and Laura Facci
Affiliation:
Keywords: Mitogen-activated protein kinase, c-Jun N-terminal kinase, phosphorylation, neurodegeneration, Alzheimer's disease, Parkinson's disease, neuroprotection
Abstract: The signaling pathways which contribute to neuronal death during development, aging and disease have been extensively studied. While initial efforts focused on developmental death, increasing evidence suggests that mitogenactivated protein kinase pathways play a role in human pathology. In particular, the c-Jun N-terminal kinases (JNKs), mitogen- activated protein kinases activated by extracellular stimuli including stress, are a major focus. Knock-out mouse studies have demonstrated that removing particular JNK genes can reduce the severity in various disease scenarios, including those which are used to model Parkinsons disease and cerebral ischemia. In addition, activation of JNKs can be seen in human disease tissue. In this review we bring together the evidence for JNK being an important regulator of neuronal loss and outline the advancement of small molecule inhibitors for future therapeutic intervention.
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Cite this article as:
Philpott L. Karen and Facci Laura, MAP Kinase Pathways in Neuronal Cell Death, CNS & Neurological Disorders - Drug Targets 2008; 7 (1) . https://dx.doi.org/10.2174/187152708783885129
DOI https://dx.doi.org/10.2174/187152708783885129 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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