Theoretical basis for a pharmacology of nerve growth factor biosynthesis.

Neuronal plasticity is a term widely used to indicate a number of neuronal mechanisms that are coordinated and triggered in the peripheral and central nervous system (eNS) to overcome functional impairment due to damage evoked by disease processes and trauma. Though this term is mainly descrip­ tive for various molecular processes whose operation and nature are still unclear, we now believe that neuronal plasticity is controlled by a variety of trophic factors produced by neuronal and glial cells. Nerve growth factor (NGF) could be one of these trophic agents. Indeed, several lines of evidence assign to NGF a role as trophic factor for specific populations of central cholinergic neurons. It is currently thought that NGF might be used to prevent the progression of neurodegenerative diseases. However, its inability to cross the blood brain barrier prevents NGF from being easily used in CNS disorder therapy. One alternative that should be explored is the possibility of enhanc­ ing NGF availability via a pharmacologically induced increase of NGF biosynthesis and release in the CNS. At present, the mechanisms that regulate the synthesis and release of NGF are still unknown. These mechanisms must be characterized before drugs can be developed that will ameliorate the symptoms of neurodegenerative diseases