Association between insulin and Nrf2 signalling pathway in Alzheimer's disease: A molecular landscape

• Published in: Life sciences (1973) 2023-09, Vol.328, p.121899-121899, Article 121899
• Main Authors: Rahman, Syed Obaidur, Khan, Tahira, Iqubal, Ashif, Agarwal, Shivani, Akhtar, Mohd, Parvez, Suhel, Shah, Zahoor Ahmad, Najmi, Abul Kalam
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Heme oxygenase-1; Insulin signalling; Nuclear factor erythroid 2-related factor 2; PI3K-AKT pathway
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.121899

Insulin, a well-known hormone, has been implicated as a regulator of blood glucose levels for almost a century now. Over the past few decades, the non-glycemic actions of insulin i.e. neuronal growth and proliferation have been extensively studied. In 2005, Dr. Suzanne de La Monte and her team reported that insulin might be involved in the pathogenesis of Alzheimer's Disease (AD) and thus coined a term “Type-3 diabetes” This hypothesis was supported by several subsequent studies. The nuclear factor erythroid 2- related factor 2 (Nrf2) triggers a cascade of events under the regulation of distinct mechanisms including protein stability, phosphorylation and nuclear cytoplasmic shuttling, finally leading to the protection against oxidative damage. The Nrf2 pathway has been investigated extensively in relevance to neurodegenerative disorders, particularly AD. Many studies have indicated a strong correlation between insulin and Nrf2 signalling pathways both in the periphery and the brainbut merely few of them have focused on elucidating their inter-connective role in AD. The present review emphasizes key molecular pathways that correlate the role of insulin with Nrf2 during AD. The review has also identified key unexplored areas that could be investigated in future to further establish the insulin and Nrf2 influence in AD. [Display omitted] •The insulin dysregulation or resistance might be involved in the pathogenesis and progression of Alzheimer’s disease, often referred to as Type3-diabetes.•The key molecular pathways like Nrf2/ARE pathway, PI3K/Akt-Nrf2 pathway, Nrf2/HO-1 pathway etc. establishes the correlation between insulin and Nrf2 signaling pathways both in the periphery and the brain.•The Nrf2 triggers a cascade of events under the regulation of distinct mechanisms that lead to the protection against oxidative damage.•The potential drawbacks, especially development of malignancy, should be outweighed before targeting Nrf2 activation for neurodegeneration therapies.