Recent Advances in Drug Delivery Systems Targeting Insulin Signalling for the Treatment of Alzheimer's Disease

Punya Sachdeva, Kannan Badri Narayanan, Jitendra Kumar Sinha, Saurabh Gupta, Shampa Ghosh, Krishna Kumar Singh, Rakesh Bhaskar, Abdulmajeed G. Almutary, James H. Zothantluanga, Kranthi Kumar Kotta, Vinod Kumar Nelson, Ana Cláudia Paiva-Santos, Mosleh Mohammad Abomughaid, Mehnaz Kamal, Danish Iqbal, Mohammed Hamoud Alharbi, Awadh Aedh Almutairi, Saikat Dewanjee, Mohana Vamsi Nuli, Shanmugam VippamakulaSaurabh Kumar Jha, Shreesh Ojha, Niraj Kumar Jha

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)1169-1179
Number of pages11
JournalJournal of Alzheimer's Disease
Volume98
Issue number4
DOIs
Publication statusPublished - Apr 16 2024

Keywords

  • Alzheimer's disease
  • amyloid-beta plaques
  • antidiabetics
  • drug delivery systems
  • insulin signaling
  • intranasal drug delivery
  • metformin
  • nanoparticles
  • neurodegeneration
  • tau phosphorylation

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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