Abstract
The p75 neurotrophin receptor (p75NTR) was originally identified as a low-affinity receptor for neurotrophins. Recent studies have revealed that p75NTR can promote cell death or survival and modulate neurite outgrowth depending on the operative ligands and co-receptors. Up-regulation and ligand activation of p75NTR have been shown to be involved in neuronal cell death in cultured cells and animal models of neurodegenerative diseases. The levels of proneurotrophins, which bind to p75NTR to promote neuronal death, have been found to be increased in postmortem brains of patients with Alzheimers disease. Furthermore, there is some evidence for the involvement of this molecule in psychiatric diseases, such as depression and schizophrenia. Mice lacking p75NTR have been shown to have several alterations in central nervous system and cognitive function. Notably, recent progress in genome-based drug discovery has enabled the identification of peptides and non-peptide small molecules targeting p75NTR, which may be potentially beneficial in the treatment of neuropsychiatric diseases. In this review, we focus on recent findings on p75NTR as a therapeutic target for neuropsychiatric diseases.
Keywords: p75NTR, neurotrophin, proneurotrophin, depression, schizophrenia, Alzheimer's disease, drug discovery, knockout (KO) mouse
Current Molecular Pharmacology
Title: p75NTR as a Therapeutic Target for Neuropsychiatric Diseases
Volume: 2
Author(s): Takashi Fujii and Hiroshi Kunugi
Affiliation:
Keywords: p75NTR, neurotrophin, proneurotrophin, depression, schizophrenia, Alzheimer's disease, drug discovery, knockout (KO) mouse
Abstract: The p75 neurotrophin receptor (p75NTR) was originally identified as a low-affinity receptor for neurotrophins. Recent studies have revealed that p75NTR can promote cell death or survival and modulate neurite outgrowth depending on the operative ligands and co-receptors. Up-regulation and ligand activation of p75NTR have been shown to be involved in neuronal cell death in cultured cells and animal models of neurodegenerative diseases. The levels of proneurotrophins, which bind to p75NTR to promote neuronal death, have been found to be increased in postmortem brains of patients with Alzheimers disease. Furthermore, there is some evidence for the involvement of this molecule in psychiatric diseases, such as depression and schizophrenia. Mice lacking p75NTR have been shown to have several alterations in central nervous system and cognitive function. Notably, recent progress in genome-based drug discovery has enabled the identification of peptides and non-peptide small molecules targeting p75NTR, which may be potentially beneficial in the treatment of neuropsychiatric diseases. In this review, we focus on recent findings on p75NTR as a therapeutic target for neuropsychiatric diseases.
Export Options
About this article
Cite this article as:
Fujii Takashi and Kunugi Hiroshi, p75NTR as a Therapeutic Target for Neuropsychiatric Diseases, Current Molecular Pharmacology 2009; 2 (1) . https://dx.doi.org/10.2174/1874467210902010070
DOI https://dx.doi.org/10.2174/1874467210902010070 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
Call for Papers in Thematic Issues
Common mechanisms underpinning neurodevelopmental disorders and psychiatric diseases
A growing number of large-scale epidemiologic studies has strongly suggested that common mechanisms may be shared by aberrant brain development and psychiatric disorders. There is now an appreciation of synergic roles of genetic variants and environmental stress which profoundly affect the genome integrity and reshape brain development. This can lead ...read more
- 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
-
Cancer Stem Cells in Prostate Cancer Chemoresistance
Current Cancer Drug Targets Overview of Mechanisms of Cancer Stem Cell Drug Resistance
Current Signal Transduction Therapy Lipid Modulation of Intravascular and Cellular Sodium Handling:Mechanistic Insights and Potential Clinical Implications
Current Vascular Pharmacology Ultrasound Assisted Synthesis of 2-alkynyl Pyrazolo[1,5-a]pyrimidines as Potential Anti-cancer Agents
Letters in Drug Design & Discovery Heterogeneity Amongst 5-HT3 Receptor Subunits: Is this Significant?
Current Molecular Medicine Signal Transduction Therapy Targeting Apoptosis Pathways in Cancers
Current Signal Transduction Therapy The Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP): A New Rodent Model to Test Palliative and Neuroprotective Agents for Parkinsons disease
Current Pharmaceutical Design Potassium Channels: Novel Emerging Biomarkers and Targets for Therapy in Cancer
Recent Patents on Anti-Cancer Drug Discovery Effect of Phosphorylation and Aggregation on Tau Binding to Dna
Protein & Peptide Letters Involvement of Trace Elements in the Pathogenesis of Prion Diseases
Current Pharmaceutical Biotechnology Anti-GD2 Antibody Therapy for GD2-Expressing Tumors
Current Cancer Drug Targets Thalidomide as an Antiangiogenic Drug in the Treatment of Multiple Myeloma
Letters in Drug Design & Discovery A Second Look into the Oxidant Mechanisms in Alzheimers Disease
Current Neurovascular Research Regulation of Angiogenesis by Th1- and Th2-Type Cytokines
Current Pharmaceutical Design Proteases as Anti-Cancer Targets - Molecular and Biological Basis for Development of Inhibitor-Like Drugs Against Cancer
Anti-Cancer Agents in Medicinal Chemistry Suicidal Inactivation of Methemoglobin by Generation of Thiyl Radical: Insight into NAC Mediated Protection in RBC
Current Molecular Medicine MAPKs and Their Inhibitors in Neuronal Differentiation
Current Enzyme Inhibition Targeting Transcription Factors for Cancer Therapy
Current Pharmaceutical Design Reactivity-Based Drug Discovery Using Vitamin B6-Derived Pharmacophores
Mini-Reviews in Medicinal Chemistry Regulation and Quantification of Cellular Mitochondrial Morphology and Content
Current Pharmaceutical Design