Neurotrophic factors in peripheral neuropathies: therapeutic implications. 1999

S C Apfel
Dept. of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. apfel@aecom.yu.edu

Neurotrophic factors are proteins which promote the survival of specific neuronal populations. Many have other physiological effects on neurons such as inducing morphological differentiation, enhancing nerve regeneration, stimulating neurotransmitter expression, and otherwise altering the physiological characteristics of neurons. These properties suggest that neurotrophic factors are highly promising as potential therapeutic agents for neurological disease. Neurotrophic factors will most likely be applied to the peripheral nervous system initially, since there are fewer problems for large proteins to gain access to peripheral neurons. Many of the most intensively studied factors are active in the peripheral nervous system. These include the neurotrophins (nerve growth factor, brain derived neurotrophic factor, neurotrophin-3, neurotrophin-4/5), the insulin like growth factors, ciliary neurotrophic factor, and glial cell derived neurotrophic factor and its related proteins. The biology of these factors and their receptors in the peripheral nervous system is reviewed here. We also review data suggesting that abnormal availability of some factors may contribute towards the pathogenesis of certain types of peripheral neuropathy. Finally, the pre-clinical data suggesting that individual factors might be effective in treating neuropathy is reviewed, along with data relating to possible side effects of neurotrophic factor therapy. Several factors have already entered clinical trials with variable success. The data from these trials is reviewed as well.

UI MeSH Term Description Entries
D008959 Models, Neurological Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Neurologic Models,Model, Neurological,Neurologic Model,Neurological Model,Neurological Models,Model, Neurologic,Models, Neurologic
D009414 Nerve Growth Factors Factors which enhance the growth potentialities of sensory and sympathetic nerve cells. Neurite Outgrowth Factor,Neurite Outgrowth Factors,Neuronal Growth-Associated Protein,Neuronotrophic Factor,Neurotrophic Factor,Neurotrophic Factors,Neurotrophin,Neurotrophins,Growth-Associated Proteins, Neuronal,Neuronal Growth-Associated Proteins,Neuronotrophic Factors,Neurotrophic Protein,Neurotrophic Proteins,Proteins, Neuronal Growth-Associated,Factor, Neurite Outgrowth,Factor, Neuronotrophic,Factor, Neurotrophic,Factors, Nerve Growth,Factors, Neurite Outgrowth,Factors, Neuronotrophic,Factors, Neurotrophic,Growth Associated Proteins, Neuronal,Growth-Associated Protein, Neuronal,Neuronal Growth Associated Protein,Neuronal Growth Associated Proteins,Outgrowth Factor, Neurite,Outgrowth Factors, Neurite,Protein, Neuronal Growth-Associated
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009437 Neuralgia Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. Nerve Pain,Neurodynia,Paroxysmal Nerve Pain,Neuralgia, Atypical,Neuralgia, Iliohypogastric Nerve,Neuralgia, Ilioinguinal,Neuralgia, Perineal,Neuralgia, Stump,Neuralgia, Supraorbital,Neuralgia, Vidian,Neuropathic Pain,Atypical Neuralgia,Atypical Neuralgias,Iliohypogastric Nerve Neuralgia,Iliohypogastric Nerve Neuralgias,Ilioinguinal Neuralgia,Ilioinguinal Neuralgias,Nerve Neuralgia, Iliohypogastric,Nerve Neuralgias, Iliohypogastric,Nerve Pain, Paroxysmal,Nerve Pains,Nerve Pains, Paroxysmal,Neuralgias,Neuralgias, Atypical,Neuralgias, Iliohypogastric Nerve,Neuralgias, Ilioinguinal,Neuralgias, Perineal,Neuralgias, Stump,Neuralgias, Supraorbital,Neuralgias, Vidian,Neurodynias,Neuropathic Pains,Pain, Nerve,Pain, Neuropathic,Pain, Paroxysmal Nerve,Pains, Nerve,Pains, Neuropathic,Pains, Paroxysmal Nerve,Paroxysmal Nerve Pains,Perineal Neuralgia,Perineal Neuralgias,Stump Neuralgia,Stump Neuralgias,Supraorbital Neuralgia,Supraorbital Neuralgias,Vidian Neuralgia,Vidian Neuralgias
D010523 Peripheral Nervous System Diseases Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. Peripheral Nerve Diseases,Peripheral Neuropathies,PNS (Peripheral Nervous System) Diseases,PNS Diseases,Peripheral Nervous System Disease,Peripheral Nervous System Disorders,Nerve Disease, Peripheral,Nerve Diseases, Peripheral,Neuropathy, Peripheral,PNS Disease,Peripheral Nerve Disease,Peripheral Neuropathy
D003929 Diabetic Neuropathies Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325) Diabetic Amyotrophy,Diabetic Autonomic Neuropathy,Diabetic Neuralgia,Diabetic Polyneuropathy,Neuralgia, Diabetic,Asymmetric Diabetic Proximal Motor Neuropathy,Diabetic Asymmetric Polyneuropathy,Diabetic Mononeuropathy,Diabetic Mononeuropathy Simplex,Diabetic Neuropathy, Painful,Mononeuropathy, Diabetic,Symmetric Diabetic Proximal Motor Neuropathy,Amyotrophies, Diabetic,Amyotrophy, Diabetic,Asymmetric Polyneuropathies, Diabetic,Asymmetric Polyneuropathy, Diabetic,Autonomic Neuropathies, Diabetic,Autonomic Neuropathy, Diabetic,Diabetic Amyotrophies,Diabetic Asymmetric Polyneuropathies,Diabetic Autonomic Neuropathies,Diabetic Mononeuropathies,Diabetic Mononeuropathy Simplices,Diabetic Neuralgias,Diabetic Neuropathies, Painful,Diabetic Neuropathy,Diabetic Polyneuropathies,Mononeuropathies, Diabetic,Mononeuropathy Simplex, Diabetic,Mononeuropathy Simplices, Diabetic,Neuralgias, Diabetic,Neuropathies, Diabetic,Neuropathies, Diabetic Autonomic,Neuropathies, Painful Diabetic,Neuropathy, Diabetic,Neuropathy, Diabetic Autonomic,Neuropathy, Painful Diabetic,Painful Diabetic Neuropathies,Painful Diabetic Neuropathy,Polyneuropathies, Diabetic,Polyneuropathies, Diabetic Asymmetric,Polyneuropathy, Diabetic,Polyneuropathy, Diabetic Asymmetric,Simplex, Diabetic Mononeuropathy,Simplices, Diabetic Mononeuropathy
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051100 Glial Cell Line-Derived Neurotrophic Factor The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE. Glial Cell-Derived Neurotrophic Factor,Glial-Derived Neurotrophic Factor,GDNF,GDNF Growth Factor,Glial Cell-Line Derived Neurotrophic Factor,Factor, Glial-Derived Neurotrophic,Glial Cell Derived Neurotrophic Factor,Glial Cell Line Derived Neurotrophic Factor,Glial Derived Neurotrophic Factor,Growth Factor, GDNF,Neurotrophic Factor, Glial-Derived
D019208 Brain-Derived Neurotrophic Factor A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994) BDNF,Brain Derived Neurotrophic Factor,Factor, Brain-Derived Neurotrophic,Neurotrophic Factor, Brain-Derived
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