The role of neuronal growth factors in neurodegenerative disorders of the human brain.
Recent evidence suggests that neurotrophic factors that promote the survival or differentiation of developing neurons may also protect mature neurons from neuronal atrophy in the degenerating human brain. Furthermore, it has been proposed that the pathogenesis of human neurodegenerative disorders may be due to an alteration in neurotrophic factor and/or trk receptor levels. The use of neurotrophic factors as therapeutic agents is a novel approach aimed at restoring and maintaining neuronal function in the central nervous system (CNS). Research is currently being undertaken to determine potential mechanisms to deliver neurotrophic factors to selectively vulnerable regions of the CNS. However, while there is widespread interest in the use of neurotrophic factors to prevent and/or reduce the neuronal cell loss and atrophy observed in neurodegenerative disorders, little research has been performed examining the expression and functional role of these factors in the normal and diseased human brain. This review will discuss recent studies and examine the role members of the nerve growth factor family (NGF, BDNF and NT-3) and trk receptors as well as additional growth factors (GDNF, TGF-alpha and IGF-I) may play in neurodegenerative disorders of the human brain.
Connor
B
B
Department of Pharmacology, Faculty of Medicine and Health Science, University of Auckland, New Zealand.
Dragunow
M
M
D001921:Brain / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D009410:Nerve Degeneration / Q000503:physiopathology*; D009414:Nerve Growth Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D020933:Neurotrophin 3; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D016211:Transforming Growth Factor alpha / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D016211:Transforming Growth Factor alpha; D007334:Insulin-Like Growth Factor I; D020794:Receptor Protein-Tyrosine Kinases