Abstract
The endogenous polyamines (spermine, spermidine, and putrescine) are present at relatively high concentrations in the mammalian brain and play crucial roles in a variety of aspects of cell functioning. Stroke is the third most common cause of death and the leading cause of disability among adults in the western world. Brain polyamine levels change dramatically following cerebral ischaemia. Polyamines may be involved in the pathophysiological processes underlying brain ischaemia through several possible mechanisms. These include direct effects on ion channels and receptors modulating potassium, and most importantly calcium trafficking, or through the production of toxic metabolites. Considerable evidence shows that the noncompetitive polyamine antagonists, ifenprodil and eliprodil, are neuroprotective. Interestingly, novel polyamine analogues, such as N1-dansylspermine, BU36b, and BU43b, have also recently been shown to have neuroprotective potential. The exact mechanisms of the neuroprotection afforded by the polyamine antagonists and their clinical applicability is worthy of further study.
Keywords: Polyamine, brain, CNS, stroke, therapeutics, neurotoxicity, NMDA
Current Medicinal Chemistry
Title: Polyamines in the Brain: Distribution, Biological Interactions, and their Potential Therapeutic Role in Brain Ischaemia
Volume: 14 Issue: 17
Author(s): Jun Li, Karen M. Doyle and Turgut Tatlisumak
Affiliation:
Keywords: Polyamine, brain, CNS, stroke, therapeutics, neurotoxicity, NMDA
Abstract: The endogenous polyamines (spermine, spermidine, and putrescine) are present at relatively high concentrations in the mammalian brain and play crucial roles in a variety of aspects of cell functioning. Stroke is the third most common cause of death and the leading cause of disability among adults in the western world. Brain polyamine levels change dramatically following cerebral ischaemia. Polyamines may be involved in the pathophysiological processes underlying brain ischaemia through several possible mechanisms. These include direct effects on ion channels and receptors modulating potassium, and most importantly calcium trafficking, or through the production of toxic metabolites. Considerable evidence shows that the noncompetitive polyamine antagonists, ifenprodil and eliprodil, are neuroprotective. Interestingly, novel polyamine analogues, such as N1-dansylspermine, BU36b, and BU43b, have also recently been shown to have neuroprotective potential. The exact mechanisms of the neuroprotection afforded by the polyamine antagonists and their clinical applicability is worthy of further study.
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Cite this article as:
Jun Li , Karen M. Doyle and Turgut Tatlisumak , Polyamines in the Brain: Distribution, Biological Interactions, and their Potential Therapeutic Role in Brain Ischaemia, Current Medicinal Chemistry 2007; 14 (17) . https://dx.doi.org/10.2174/092986707781058841
DOI https://dx.doi.org/10.2174/092986707781058841 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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