Neurotrophic factors: from molecule to man

RM Lindsay, SJ Wiegand, CA Altar… - Trends in neurosciences, 1994 - cell.com
RM Lindsay, SJ Wiegand, CA Altar, PS DiStefano
Trends in neurosciences, 1994cell.com
Recent advances m the understanding of the physiological rob of nerve growth factor (NGF)
have raised the question of whether neurotrophlc factors ml&ht have c/mlca/potential in the
treatment of neurodegenerabve disease or nerve trauma Although NGF was first
characterized as a target-denved sumval factor for developing sympathehc and sensory
neurons, it is now dear that it plays an important role in the maintenance and regeneration of
mature peripheral neurons However, the highly restricted specificity of NGF for sympathetic …
Recent advances m the understanding of the physiological rob of nerve growth factor (NGF) have raised the question of whether neurotrophlc factors ml&ht have c/mlca/potential in the treatment of neurodegenerabve disease or nerve trauma Although NGF was first characterized as a target-denved sumval factor for developing sympathehc and sensory neurons, it is now dear that it plays an important role in the maintenance and regeneration of mature peripheral neurons However, the highly restricted specificity of NGF for sympathetic neurons, subpopu/atlons of neura/-crest-denved sensory neurons, and stnata/and basa/forebram cho/mer&ic neurons has, for almost two decades, stimulated the search for other neurotrophlc factors that might act on the many classes of neurons that do not respond to NCF In this artde, the biology of the recently discovered NGF-re/ated family of neurotrophlc factors and c# lary neurotrophtc factor and their receptors are reviewed, especial/)/in the context of the therapeutic potential of these factors/n the treatment of neurologmal disorders of the CNS
The recent cloning of bram-denved neurotrophc factor 1 (BDNF) revealed not only that this polypepbde rs closely related to NGF, but also led to the discovery of a larger gene famdy the neurotrophlns In addibon to NGF and BDNF, thJs famdy of small (-13 kDa) highly basic (pl 9-10 5) proteins now includes neurotrophm-3 (NT-3) and NT-4/5 (see Ref 2 for revrew) Quite independently, the past three years have seen the discovery of a famdy of receptor tyrosme kmases, the Trks, which are h~ ghaffinity neurotrophin receptors (see Ref 3 for review) The current knowledge of the specificity of each of the neurotrophms for the receptors encoded by the three known mammahan trkgenes, trkA, trkB and trkC, is shown fn Fig 1 Each trk gene rs capable of producing multiple transcripts In addlbon to proteins that display vanants in their kmase domains, TrkB and TrkC receptors also exist as truncated proterns which lack intracellular kinase domains The neurotrophms exist naturally as homodlmers (and possibly heterodtmers) and, as with hgands for other
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