Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer's disease indicate possible resistance to IGF-1 and insulin signalling.

By A. Moloney, Rebecca J. Griffin, Suzanne Timmons, R. O’Connor, R. Ravid, C. O'Neill. Neurobiology of Aging, 2010

743 citations recorded by the source corpus.

Subfields: Endocrinology, Diabetes and Metabolism, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6ba2d56fc688a87bd48366afe81a96c467947de5

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In Endocrinology, Diabetes and Metabolism

1. C. Zhong
2. Zhichun Chen

In Molecular Biology

1. John Q. Trojanowski
2. Sérgio T. Ferreira
3. C. Zhong
4. F. D. De Felice
5. Zhichun Chen

Citations in the corpus

• Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. (2012, background): “A number of the findings at upstream levels of the pathway are consistent with insulin resistance as defined above, notably decreased basal activation of IRs (28); reduced insulin binding of the IR, even early in the disorder (27); increased serine phosphorylation (pS) of IRS-1 (29, 33, 37); and red”
• Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. (2013, background): “The study have reported that AD exhibits the decrease in CSF insulin levels, the ratios of CSF insulin over plasma insulin, IR expression, and the increase in fasting plasma insulin levels (Moloney et al., 2010).”
• Inflammation, Defective Insulin Signaling, and Mitochondrial Dysfunction as Common Molecular Denominators Connecting Type 2 Diabetes to Alzheimer Disease (2014, background): “AD brains exhibit defective insulin signaling, altered levels and/or aberrant activation of components of the insulin signaling pathway, and, importantly, decreased responsiveness to insulin (35,36,38).”
• Protection of synapses against Alzheimer's-linked toxins: Insulin signaling prevents the pathogenic binding of Aβ oligomers (2009, background): “Significantly, the marked loss of IRs from synaptic plasma membranes seen in response to ADDLs (9) has been confirmed in neuropathology studies showing that IRs are lost from dendrites in AD brain (49).”
• An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease- associated Aβ oligomers. (2012, positive): “However, since IRs are removed from the neuronal membrane in AD brains (4) and in cultured neurons exposed to oligomers (9), use of insulin itself might not be the most effective way to combat AD.”
• Neural mechanisms of ageing and cognitive decline (2010, background): “In patients with Alzheimer's disease, there is evidence of reduced expression of components of the IGF signalling pathwa”