Neurotrophins, neuroprotection and the blood-brain barrier.
Small molecule drugs have not been effective neuroprotective agents in either the acute treatment of stroke or the chronic treatment of neurodegeneration. Thus, it is time to consider large molecule drugs such as recombinant neurotrophins. However, like many of the small molecules, neurotrophins do not cross the brain capillary endothelial wall, which forms the blood-brain barrier (BBB). Neurotrophins can be made transportable across the BBB by using chimeric peptide brain drug targeting technology, in which a neurotrophin is reformulated by fusion to a transport vector. The latter is a peptide or peptidomimetic monoclonal antibody that undergoes receptor-mediated transcytosis through the BBB, and acts as a 'molecular Trojan horse'. Neurotrophin chimeric peptides are highly neuroprotective following delayed intravenous administration, in both global and focal brain ischemia.
Pardridge
William M
WM
Department of Medicine, UCLA Warren Hall, 900 Veteran Avenue, Los Angeles, CA 90024, USA. wpardridge@mednet.ucla.edu
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents