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.
Export Options
About this article
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Regenerative Medicine: Does Erythropoietin have a Role?
Current Pharmaceutical Design Thalidomide as an Antiangiogenic Drug in the Treatment of Multiple Myeloma
Letters in Drug Design & Discovery Removing Protein Aggregates: The Role of Proteolysis in Neurodegeneration
Current Medicinal Chemistry Antibody-Targeted Immunoliposomes for Cancer Treatment
Mini-Reviews in Medicinal Chemistry Disintegrins from Snake Venoms and their Applications in Cancer Research and Therapy
Current Protein & Peptide Science Evolving Therapeutic Targets in Ischemic Stroke: A Concise Review
Current Drug Targets MicroRNAs Involved in Oxidative Stress Processes Regulating Physiological and Pathological Responses
MicroRNA Novel Natural and Synthetic Ligands of the Endocannabinoid System
Current Medicinal Chemistry Role of mTOR in Hematological Malignancies
Current Cancer Therapy Reviews Phytometabolites Targeting the Warburg Effect in Cancer Cells: A Mechanistic Review
Current Drug Targets Anti-cancer Potential of Phyto-alkaloids: A Prospective Review
Current Cancer Therapy Reviews Transdermal Nutraceuticals Delivery System for CNS Disease
CNS & Neurological Disorders - Drug Targets Mitochondria: Prospective Targets for Neuroprotection in Parkinson's Disease
Current Pharmaceutical Design Possible Neuroprotective Strategies in ALS
Current Neuropharmacology The Crosstalk of RAS with the TGF-β Family During Carcinoma Progression and its Implications for Targeted Cancer Therapy
Current Cancer Drug Targets Neurokinin Receptors and Subtypes as Potential Targets in Breast Cancer: Relevance to Bone Marrow Metastasis
Drug Design Reviews - Online (Discontinued) Novel Lactulose and Melibiose Targeting Autophagy to Reduce PolyQ Aggregation in Cell Models of Spinocerebellar Ataxia 3
CNS & Neurological Disorders - Drug Targets A Review of Pediatric Mediastinal Masses and Castlemans Disease
Current Pediatric Reviews New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer
Current Pharmaceutical Design The Therapeutic Target Hsp90 and Cancer Hallmarks
Current Pharmaceutical Design