JNK signalling: a possible target to prevent neurodegeneration

Details

Serval ID
serval:BIB_03F7FB909B6A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
JNK signalling: a possible target to prevent neurodegeneration
Journal
Current Pharmaceutical Design
Author(s)
Borsello  T., Forloni  G.
ISSN
1873-4286 (Electronic)
Publication state
Published
Issued date
2007
Volume
13
Number
18
Pages
1875-86
Notes
Journal Article
Research Support, Non-U.S. Gov't
Review
Abstract
The c-Jun N-terminal kinases (JNK) belong to the subfamily of mitogen-activated protein kinase (MAPK). JNK is an important transducing enzyme that is involved in many facets of cellular regulation including gene expression, cell proliferation and programmed cell death. The activation of JNK pathways is critical for naturally occurring cell death during development as well as for pathological death associated with neurodegenerative diseases. Initial research concentrated on defining the components and organization of JNK signalling cascades, but more recent studies see JNK as a target to prevent cell death. Several in vitro and in vivo studies have reported alterations of JNK pathways potentially associated with neuronal death in Parkinson's and Alzheimer's disease. So efforts are now aimed at developing chemical inhibitors of this pathway. These have proved effective in vivo, reducing brain damage and some of the symptoms of arthritis in animal models. An alternative cell penetrating peptide approach is now available, with the identification of the JNK permeable peptide inhibitor, which modifies JNK action rather than activation, preventing neuronal death with unprecedented specificity and efficacy in several experimental conditions, including two animal models of ischemia. In this review we examine in detail the role of JNK in neurodegeneration, particularly in Alzheimer's and Parkinson's disease. The possibility of intervention on the JNK pathway as a therapeutic approach is also illustrated.
Keywords
Alzheimer Disease/drug therapy/metabolism/pathology Amyloid beta-Protein/metabolism Animals Apoptosis/*drug effects Disease Models, Animal Humans JNK Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism MAP Kinase Signaling System/*drug effects Mice Neurodegenerative Diseases/*drug therapy/enzymology/metabolism/pathology Neurons/*drug effects/enzymology/metabolism/pathology Neuroprotective Agents/*pharmacology/therapeutic use Parkinson Disease/drug therapy/metabolism/pathology Protein Kinase Inhibitors/*pharmacology/therapeutic use
Pubmed
Web of science
Create date
24/01/2008 14:19
Last modification date
20/08/2019 12:25
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