Growth Hormone and Insulin-Like Growth Factor-I in Alzheimer′sDisease

摘要

Alzheimer's disease (AD) is a major public health issue in the ageing population. For decades, research focusedon studies using neurochemistry and biochemistry to understand the mechanisms underlying this disease. Recently,emerging evidence supports the concept that AD is also a disorder of metabolic degeneration. Amyloid beta-peptide iscentral to the pathogenesis of AD, and the AD brain is under intense oxidative stress, including membrane lipidperoxidation. Amyloid beta-peptide causes oxidative stress and neurotoxicity to neurons. Neurochemical changes in thebrain from patients with AD indicate multiple disturbances and it seems likely that the changes are secondary to morefundamental changes into the brain. Based on decreased IGF-I concentrations in AD, some authors have suggested thatdisrupted IGF-I input to the brain may be involved in the pathogenesis of amyloidosis and changed IGF-I signalling maypotentially lead to amyloidosis. Disrupting IGF-I signalling in the coroid plexus is sufficient to trigger pathologicalchanges as those observed in AD and brain -amyloid increases as consequence of its lower clearance. The IGF-I is apotent neurotrophic as well neuroprotective factor found in the brain with a wide range of actions in both central andperipheral nervous system. IGF-I is a critical promoter of brain development and neuronal survival and plays a role inneuronal rescue during degenerative diseases. So, an emerging clinical targets for improving the quality of life withageing or for improving clinical manifestations of AD may be activation of GH/IGF-I that rejuvenate the axis to result inoverall physiological benefit, with a potential of prevent or reverse detrimental age-related or AD changes in the brain.