12 November 2009

Potential roles of insulin and IGF-1 in Alzheimer’s disease

Aging is characterized by a significant decline of metabolic and hormonal functions, which often facilitates the onset of severe age-associated pathologies. One outstanding example of this is the reported association of deranged signaling by insulin and insulin-likegrowth- factor 1 (IGF-1) with Alzheimer’s disease (AD).
Recent compelling biological data reveal effects of insulin and IGF-1 on molecular and cellular mechanisms underlying the pathology of AD.Emerging evidence suggests that insulin and IGF-1 have important functions in the brain, including metabolic, neurotrophic, neuromodulatory and neuroendocrine actions.Insulin, IGF-1, their receptors and IGF-1-binding proteins (IGFBPs) are all present in rodent and human brain.It is now known that insulin and IGF-1 are actively
transported across the blood–brain barrier and possibly even produced locally in the brain.
In addition to the physiological activities in the brain, a wealth of data points to a potential role of the insulin– IGF-1 pathway in the pathogenesis of age-related neurodegenerative diseases, such as Alzheimer’s disease.In particular, AD patients show changes in insulin and IGF-1 levels and their response to insulin is defective.

1 comment:

  1. Consistent with these findings, work by Suzanne Craft and colleagues has shown that excessive insulin invokes synchronous increases in levels of beta amyloid and inflammatory agents. These effects are exacerbated by older age and obesity.

    See for example the following review:
    Craft, S. (2004). Insulin resistance syndrome and Alzheimer's disease: Age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiology of Aging. 26 pp65-69.

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