Small molecule activators of the Trk receptors for neuroprotection.
The neurotrophin signaling network is critical to the development and survival of many neuronal populations. Especially sensitive to imbalances in the neurotrophin system, cholinergic neurons in the basal forebrain are progressively lost in Alzheimer's disease. Therapeutic use of neurotrophins to prevent this loss is hampered, however, by a number of pharmacological challenges. These include a lack of transport across the blood-brain barrier, rapid degradation in the circulation, and difficulty in production. In this review we discuss the evidence supporting the neurotrophin system's role in preventing neurodegeneration and survey some of the pharmacological strategies being pursued to develop effective therapeutics targeting neurotrophin function.
Webster
Nicholas J G
NJ
Veterans Medical Research Foundation and VA San Diego Healthcare System, San Diego, CA 92161, USA. nwebster@ucsd.edu
Pirrung
Michael C
MC
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D006801:Humans; D008024:Ligands; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*
D008024:Ligands; D018696:Neuroprotective Agents; D017475:Receptors, Nerve Growth Factor