Central Nervous System Agents in Medicinal Chemistry

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Growth Hormone/Insulin-Like Growth Factor-I Axis and Insulin in Alzheimers Disease and Its Possible Treatment Usefulness

Author(s): Jose Manuel Gomez.

Abstract:

Alzheimers disease (AD) is a progressive neurodegenerative disorder characterized by insidious onset with cognitive impairment; affects mental function, and is of the amnesic type. Neuropathological analysis of AD-affected brains reveals extensive atrophy and an accumulation of neurofibrillary tangles. AD is a major public health issue in the ageing population and for decades, researches focused on 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. There is a physiological decline of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis with ageing, and the possibility that the GH/IGF-I axis is involved in cognitive deficits has been recognized for several years. The IGF-I is a potent neurotrophic as well as a neuroprotective factor found in the brain, with a wide range of actions in both the central and the peripheral nervous systems. IGF-I is a critical promoter of brain development and neuronal survival, and plays a role in neuronal rescue during degenerative diseases. The investigations of GH-releasing stimulation tests, and especially of GHRH in AD, are equivocal and in some cases contradictory. After an acetylcholinesterase inhibitor, such as rivastigmine, a drug for AD, is acutely administered, the area under the curve of the GH response to GHRH doubles, showing that is a powerful drug in the enhancement of GH release. Consequently, an emerging clinical target for improving the quality of life with ageing, or for improving the clinical manifestations of AD, may be the activation of GH/IGF-I axis , which rejuvenates it, so resulting in an overall physiological benefit, with a potential for preventing or reversing detrimental age-related or AD changes in the brain.

Keywords: Acetylcholinesterase inhibitors, Alzheimer's disease, GH-releasing stimulation tests, growth hormone, insulin, insulin- like growth factor-I

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Article Details

VOLUME: 8
ISSUE: 4
Year: 2008
Page: [267 - 274]
Pages: 8
DOI: 10.2174/187152408786848120
Price: $58