Theories on the promotion of CNS transplant integration by selective activation of presynaptic enzyme cascades: prospects for future clinical applications.
It is hypothesized that multiple parallel presynaptic enzyme cascades act concertedly to regulate synaptic plasticity. These enzyme cascades include phospholipases A2 and C, protein kinase C, calcium/calmodulin and cAMP-dependent protein kinases and adenylate cyclase. New putative neurotrophic agents are postulated based on their ability to activate these enzymes. The artificial induction and amplification of multiple presynaptic enzymes in the fetal graft-mature host CNS tissue complex should maximally augment axon growth and synaptogenesis. In turn this would lead to enhanced transplant integration and hence maximal functional neurologic restoration. These enzyme cascades could be stimulated in-vivo by the intraventricular infusion of receptor-specific and/or lipophilic neurotrophic agents as well as by the application of external electric fields. A theoretical construct is formulated for developing future grafting experimentation with the hope of ultimately applying these concepts to the amelioration of human neurodegenerative diseases.
Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland.
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Moskowitz
D000818:Animals; D002490:Central Nervous System / Q000201:enzymology / Q000254:growth & development / Q000601:surgery*; D004789:Enzyme Activation; D005333:Fetus; D006801:Humans; D008959:Models, Neurological; D009417:Nerve Tissue / Q000637:transplantation*; D009422:Nervous System Diseases / Q000601:surgery; D013569:Synapses / Q000201:enzymology