Combination of Insulin with a GLP1 Agonist Is Associated with Better Memory and Normal Expression of Insulin Receptor Pathway Genes in a Mouse Model of Alzheimer's Disease.
Here, we show that microRNA 7 (miR-7), an abundant microRNA in the brain, targets insulin receptor (INSR), insulin receptor substrate 2 (IRS-2), and insulin-degrading enzyme (IDE), key regulators of insulin homeostatic functions in the central nervous system (CNS) and the pathology of AD.
Following these discoveries, evidence of decreased brain insulin receptor number and function was reported in both clinical samples and animal models of aging and Alzheimer's disease, setting the stage for the hypothesis that neuronal insulin resistance may underlie memory loss in these conditions.
The cross-talk between NGF and insulin pathways downstream the insulin receptor suggests novel potential therapeutic targets to slow cognitive decline in AD and diabetes-related brain insulin resistance.
Across multiple samples (n = 4502), the biologically informed, mesocorticolimbic or hippocampal specific insulin receptor polygenic scores were calculated, and their ability to predict impulsivity, risk for addiction, cognitive performance and presence of Alzheimer's disease was investigated.
Parahippocampal gyrus expression of endothelial and insulin receptor signaling pathway genes is modulated by Alzheimer's disease and normalized by treatment with anti-diabetic agents.
Brain protein O-GlcNAcylation is diminished in Alzheimer's disease (AD), and OGT targets include proteins of the insulin-signaling pathway (e.g., insulin receptor susbtrate-1, IRS-1).
Insulin and the IR are also present in the brain, and since there is evidence that neuronal insulin signaling regulates synaptic plasticity and that it is impaired in disease, this pathway might be the key to protection or reversal of symptoms, especially in Alzheimer's disease.
Reported evidence shows that vascular risk factors are associated with AD, particularly in the development of protein aggregation, inflammation, oxidative stress, neuronal dysfunction, and disturbances in signaling pathways, with insulin receptor signaling being a common alteration between MetS and AD.
Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer's disease?
However, when the samples were analyzed separately according to the region of the brain, there was a significant upregulation of INSR expression in the hippocampus and the entorhinal cortex in the AD patient group.
Alzheimer's disease (AD) is associated with reduced insulin level and impairment of insulin receptor (IR) signaling in the brain, which correlates to amyloid pathology, neuroinflammation, and synaptic neurotoxicity.
Alzheimer's disease (AD) is associated with progressive impairments in brain insulin, insulin-like growth factor (IGF), and insulin receptor substrate (IRS) signaling through Akt pathways that regulate neuronal growth, survival, metabolism, and plasticity.The intracerebral streptozotocin (i.c.
In this regard, it is of note that upregulation of plasma adiponectin (APN), a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation, has recently been associated with the severities of amyloid deposits and cognitive deficits in the elderly, suggesting that APN may enhance the risk of AD.
These results show insulin delivery to the brain by intranasal administration can be modified with agents such as albumin, may be dependent on the insulin receptor, and is not affected by an AD-like phenotype as presented by the SAMP8 mouse.
Disturbances of brain glucose uptake, glucose tolerance, glucose utilization and of the insulin/insulin receptor signaling cascade are thought to be key features of the pathophysiology of AD.
Regulation of Aβ production by glucose and insulin and effects of Aβ on the insulin receptor pathway suggest similar cellular mechanisms may exist between neuronal dysfunction in Alzheimer disease and adipose dysfunction in type 2 diabetes.