Drug Discovery Opinion

Although family history and lifestyle choices play a role, ageing is recognised to be the largest single risk factor for Alzheimer’s disease. Progression of Alzheimer’s disease is not well understood but accumulation of toxic amyloid peptides in the brain is believed to be a significant contributory factor and much research has focussed on reducing levels of these peptides. Researchers led by a team at the Salk Institute have now asked whether slowing the ageing progress might also delay the onset of Alzheimer’s disease. The insulin/insulin growth factor (IGF) signalling (IIS) pathway regulates stress resistance, and reduction of IIS has been shown to increase lifespan in worms, flies, and mice. Although reduced IGF signalling extends the life span of mice, IGF-1 infusion has also been shown to protect mice against amyloid toxicity. To address this apparent paradox, the team crossed mice that model Alzheimer’s disease with long-lived mice that have reduced IGF signalling. The animals were found to be protected from Alzheimer’s disease-like symptoms, including behavioural impairment, neuroinflammation, and neuronal loss. Although the mice continued to produce amyloid peptides, these were found to form densely packed, ordered plaques, suggesting that hyper-aggregation of more toxic soluble amyloid oligomers may explain, at least in part, the protection conferred by reduced IGF signalling.

Although previous studies have shown that IGF-1 infusion protects mice against amyloid toxicity, the growth hormone secretagogue MK-677 (ibutamoren mesylate), a potent inducer of IGF-1 secretion, was ineffective at slowing the rate of progression of Alzheimer’s disease in human patients.

IIS reduction has been found to correlate with longevity in humans – some very long-lived people have defects in components of IIS – and the present study, which is published in the journal Cell, suggests that reduction in IGF-1 signalling may be a promising strategy for the treatment of Alzheimer’s disease.

Related posts:

1. How Arthritis May Protect Against Alzheimer’s Disease Epidemiological studies have suggested that either rheumatoid arthritis itself – or the anti-inflammatory drugs used to control it – are...
2. Nicotinic α-7 Receptors in Alzheimer’s Disease – On or Off? A number of groups are developing nicotinic α-7 receptor agonists or partial agonists for the treatment of Alzheimer’s disease. It...
3. New Role for APP in Alzheimer’s Disease Cleavage of amyloid precursor protein (APP) by β- and γ-secretases into neurotoxic β-amyloid peptides is believed to play a leading...
4. Calpain Inhibitors in Models of Alzheimer’s Disease Calpains are calcium-activated cysteine proteases which, when abnormally activated, can initiate degradation of proteins essential for neuronal survival. A report...
5. Prion Protein linked to Alzheimer’s Disease Mis-folded prion proteins have been linked to a number of neurological diseases including scrapie in sheep, bovine spongiform encephalopathy (BSE,...

Related posts brought to you by Yet Another Related Posts Plugin.

 Email This Post

This entry was posted on Tuesday, December 15th, 2009 at 8:27 am and is filed under News. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.