W. Pan, A.J. Kastin

Regeneration of the central nervous system (CNS) encounters the obstacles of inefficient delivery and degradation of neurotrophic molecules when used as therapeutic reagents. Although the blood-brain barrier (BBB) prevents free permeation of enzymes and neurotrophic proteins, it permits selective permeation of certain peptides and proteins by way of specific transport systems. Here, two scenarios are presented: delivery of lysosome enzymes to treat lysosomal storage diseases affecting the brain, and delivery of neurotrophins and neurophic peptides to rescue neuronal cell death after CNS trauma and secondary degeneration. The goals are to determine the pharmacokinetics of these proteins after peripheral delivery by intravenous injection, to identify the mechanisms of transport, and to effectively enhance BBB penetration by use of the transport systems present at the cerebral endothelial cells. Regulation of the transport systems in pathological conditions and by pharmacological manipulation, therefore, can exert a significant impact in the treatment of CNS disorders.

Keywords (Optional): 
blood-brain barrier
neurotrophic protein
SENS Research Themes: 
Ending Aging: