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.
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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 |
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