Abstract：
:Nerve growth factor (NGF) and other members of the neurotrophin family are critical for the survival and differentiation of neurons and have been implicated in the pathophysiology of numerous disease states. Although the therapeutic potential of neurotrophins has generated much excitement over the past decade, inconvenient pharmacokinetics and adverse side-effect profiles have limited the clinical usefulness of neurotrophic factors themselves. Compounds that mimic neurotrophin signaling and overcome the pharmacokinetic and side-effect barriers may have greater therapeutic potential. Here, we review the progress to date of clinical trials with direct neurotrophin modulators and describe alternative strategies to target (modulate) neurotrophin production and/or their signal transduction pathways. Particular emphasis is placed on small molecules that are able to modulate neurotrophin function in diseases of the nervous system. These alternative strategies show promise in preclinical studies, with some advancing into clinical development. Moreover, the recognition that clinically effective therapeutics, such as antidepressants and immunophilin ligands, can modulate neurotrophin function suggests that the concept of small molecule therapeutics that promote neurotrophic function may still be viable.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Price RD,Milne SA,Sharkey J,Matsuoka Ndoi
10.1016/j.pharmthera.2007.03.005subject
Has Abstractpub_date
2007-08-01 00:00:00pages
292-306issue
2eissn
0163-7258issn
1879-016Xpii
S0163-7258(07)00067-8journal_volume
115pub_type
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