Small molecule and protein-based neurotrophic ligands: agonists and antagonists as therapeutic agents

The neurotrophins are proteins of a growth factor family that affect the su rvival, growth and/or differentiation of neurones and several other populat ions derived from the neuroectoderm Neurotrophins and their receptors are i mportant targets for therapy of human disease, with potential applications ranging from treatment of chronic or acute neurodegeneration, to pain or ca ncer. Several neurotrophins have been used clinically. However, they are po or pharmacological agents because of drawbacks inherent to proteins when us ed as drugs. Consequently, several pharmacological agents and approaches ha ve been patented to exploit these important targets. Amongst the pharmacolo gical agents that do not act directly via neurotrophin receptors we include those that modulate or induce local expression of neurotrophins, immunophi lins and other agents with neurotrophic-like activity. These are usually ag onistic agents. Amongst compounds that bind to and act via neurotrophin rec eptors we include peptide analogues and peptidomimetics of neurotrophins of anti-neurotrophin receptor antibodies. These agents can be agonistic or an tagonistic. Other approaches involve antagonists of the neurotrophins thems elves, usually large receptor-derived peptides as decoy docking sites. Smal l molecule, non-peptide synthetic agonists and antagonists of either neurot rophins or neurotrophin receptors will be valuable therapeutic agents for d iseases that have markets worth billions of US dollars. Consequently, it is not surprising that some patents have made similar claims both in composit ions of matter and in indications.