AI Article Synopsis

  • Alzheimer's disease (AD) is linked to insulin signaling dysfunction, which has been discovered to play a significant role in neuron survival and cognitive function, challenging earlier assumptions about insulin's relevance in the brain.
  • Key molecules like GSK-3β, Akt, PI3K, and IRS are involved in insulin signaling, and their irregularities can lead to insulin resistance, which may contribute to the development of AD alongside oxidative stress and neuroinflammation.
  • Innovative drug delivery methods, such as oral insulin, nanoparticles, and intranasal administration, are being explored to specifically target insulin signaling as a potential treatment for AD, highlighting possible therapeutic advancements.

Article Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of neurofibrillary tangles and amyloid-β plaques. Recent research has unveiled the pivotal role of insulin signaling dysfunction in the pathogenesis of AD. Insulin, once thought to be unrelated to brain function, has emerged as a crucial factor in neuronal survival, synaptic plasticity, and cognitive processes. Insulin and the downstream insulin signaling molecules are found mainly in the hippocampus and cortex. Some molecules responsible for dysfunction in insulin signaling are GSK-3β, Akt, PI3K, and IRS. Irregularities in insulin signaling or insulin resistance may arise from changes in the phosphorylation levels of key molecules, which can be influenced by both stimulation and inactivity. This, in turn, is believed to be a crucial factor contributing to the development of AD, which is characterized by oxidative stress, neuroinflammation, and other pathological hallmarks. Furthermore, this route is known to be indirectly influenced by Nrf2, NF-κB, and the caspases. This mini-review delves into the intricate relationship between insulin signaling and AD, exploring how disruptions in this pathway contribute to disease progression. Moreover, we examine recent advances in drug delivery systems designed to target insulin signaling for AD treatment. From oral insulin delivery to innovative nanoparticle approaches and intranasal administration, these strategies hold promise in mitigating the impact of insulin resistance on AD. This review consolidates current knowledge to shed light on the potential of these interventions as targeted therapeutic options for AD.

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Source
http://dx.doi.org/10.3233/JAD-231181DOI Listing

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