Oxiaditive mediated neurodegeneration in alzheimer's diseasemelatonin and related indoles as neuroprotective agents

Resumen

Many of recent advances in AD from the study of a 40-42 amino acid peptide called amyloid beta protein (Ab), as the essential pathologic marker of the disorder (glenner and Wong, 1984; Masters et al., 1985). Studies by the principal investigator and by other scientists have shown that Ab is central to the process of neurodegeneration in AD by initiating the production of partially reduced oxygen species and damaging essential macromolecules in the CNS. A growing body of literature links these destructive oxiadative processes with some neurodegenerative aspects of AD. This thesis explores the hypothesis that melatonin and related indoles can be uses as potential therapeutic agents in Alzeimer's disease (AD). Novel findigs related to the free radical scavenging and antioxidtive properties of melatonin are presented showing a high degree of neuroprotection in several AD paradigms. The hormone efficacy and the likely mechanisms involved in its ability to reduce neuronal damage mediated by oxygen-based reactive species in AD models of neurodegeneration are investigated and discussed. Experimetal data is presented and discussed suggesting that besides the direct scaveging properties and indirect antioxidant actions of melatonin, its ability to protect neurons probably also stems from novel antiamyloidogenic properties of the hormone. Melatonin and some related infole analogues are also unique because of the ease with they pass through the blood-brain barrier and has distinct physiological relationships to the aging process.