Neurotrophic factors as pharmacological agents for the treatment of injured auditory neurons.
Mature auditory neurons degenerate in response to a loss of target-derived trophic factors. Neurotrophic factors influence the health and viability of auditory neurons. This suggests that neurotrophic factors can be used as therapeutic agents to prevent neuronal cell death and to initiate repair of damaged neuronal processes in the injured auditory system. Both in vitro and in vivo experiments have been performed to determine which of the vast array of neurotrophic factors affect mature auditory neurons and how they can be delivered to the sites of injury within the auditory system. Neurotrophin 3 was found to be a major survival factor for auditory neurons. Brain-derived neurotrophic factor is a minor survival factor for auditory neurons and nerve growth factor, although not promoting survival, does elicit the repair of neuronal processes. Fibroblast growth factor 2, transforming growth factor beta 1 and ciliary neurotrophic factor function as injury-response factors in the auditory system. Combination of different classes of growth factors has an additive effect on neuronal survival. Growth factors may be able to be delivered to sites of injury within the cochlea by either direct perfusion or gene therapy (e.g. a defective virus expressing a growth factor gene).
Van De Water
T R
TR
Department of Otolaryngology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Staecker
H
H
Ernfors
P
P
Moonen
G
G
Lefebvre
P P
PP
D000818:Animals; D003051:Cochlea / Q000378:metabolism; D006801:Humans; D009410:Nerve Degeneration; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D000159:Vestibulocochlear Nerve / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins