Polyamines in neurotrauma. Ubiquitous molecules in search of a function.
In spite of their abundance, the function of PAs in the adult nervous system remains enigmatic. It is postulated that after trauma, the induction of polyamine metabolism (i.e. the polyamine response), which is inherently transient, is an integral part of a protective biochemical program that is essential for neuronal survival. Several functions ascribed to PAs may assume importance in cellular defense. Thus, regulation of the ionic environment, modulation of signal pathways, control of cellular Ca2+ homeostasis, inhibition of lipid peroxidation, and interaction with nucleic acids are all putative sites for PA action. During maturation, the CNS, unlike the peripheral nervous system, undergoes changes which result in the expression of an incomplete polyamine response after trauma. This may be due to an altered pattern of gene expression, and/or restrictive compartmentalization of the PAs and their metabolizing enzymes. Induction of this partial polyamine response after injury results in a sustained accumulation of putrescine, which by itself may be harmful, without the concomitant increase in spermidine and spermine. Administration of exogenous PAs after trauma exerts a neuroprotective effect. Exogenous PAs are postulated to gain access into cells via an induced uptake system after trauma, and function similarly to newly synthesized PAs. Besides the injured neurons themselves, tissues which are connected or associated with these neurons may be potential targets where PAs could act to stimulate neurotrophic factor production. Based on the neuroprotective effects of PAs in laboratory animals and on their proposed role in mechanisms of neuronal survival, the development of PA-based compounds as therapeutic neuroprotective agents should be pursued.
Gilad
G M
GM
Neuropsychiatry Branch, NIMH Neurosciences Center at Saint Elizabeths, Washington, DC 20032.
Gilad
V H
VH
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011073:Polyamines / Q000378:metabolism* / Q000494:pharmacology; D013119:Spinal Cord Injuries / Q000378:metabolism*
D011073:Polyamines