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NEUROTROPHIC FACTORS AND THE DEVELOPMENT OF DRUGS TO PROMOTE MOTONEURON SURVIVAL
Author(s) -
Hughes RA,
O'Leary PD
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb01150.x
Subject(s) - neurotrophic factors , ciliary neurotrophic factor , neurotrophin , glial cell line derived neurotrophic factor , neuroscience , biology , brain derived neurotrophic factor , nerve growth factor , gdnf family of ligands , amyotrophic lateral sclerosis , growth factor , medicine , receptor , genetics , disease
SUMMARY 1. During embryonic development, neuronal populations undergo a period of naturally occurring cell death. In the vertebrate, the survival of neurons during this period is dependent upon specific neurotrophic factors. Recent advvances in in vitro and in vivo assays have led to the identification of a number of neurotrophic factors for spinal motoneurons, including brain‐derived neurotrophic factor, ciliary neurotrophic factor, fibroblast growth factors, insulin‐like growth factors and glial‐derived neurotrophic factor. 2. The presence of multiple trophic factors promoting motoneuron survival suggests either that there is significant functional redunancy between the factors or that they act in concert to produce their effects. 3. In addition to their physiological role, neurotrophic factors show tremendous clinical potential for the treatment of human neurodegenerative diseases, such as amyotrophic lateral sclerosis. However, because they are poorly absorbed across biological membranes and are unstable in plasma, the recombinant neurotrophic factors themselves are not optimally suited as drugs. One means to circumvent these problems is to use the known three‐dimensional structures of theses factors as templates to design low molecular weight compounds that retain neurotrophic activity but exhibit better pharmacokinetic properties.