The potential role of Keap1-Nrf2 pathway in the pathogenesis of Alzheimer’s disease, type 2 diabetes, and type 2 diabetes-related Alzheimer’s disease

Abstract

Kelch-like ECH associated-protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is thought to be the key regulatory process defensing oxidative stress in multiple organs. Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are both serious global health problems with high prevalence. A growing number of literatures have suggested a possible link between Keap1-Nrf2 signaling pathway and the pathological changes of T2DM, AD as well as T2DM-related AD. The current review mainly discusses how the damaged Keap1-Nrf2 signaling pathway leads to dysregulated redox molecular signaling, which may contribute to the pathogenesis of AD and T2DM-related cognitive dysfunction, as well as some compounds targeting this pathway. The further exploration of the mechanisms of this pathway could provide novel therapeutic strategies to improve cognitive function, through restoration of expression or translocation of Nrf2 and scavenging excessive free radicals.

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Fig. 1

Data availability

All data, models, and code generated or used during the study appear in the submitted article. The data will be available under reasonable request.

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Funding

This work was funded by grants from the Key Research and Development Program of Ningxia (2019BFG02017); and the National Natural Science Foundation of China (81703520).

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Yi Sun review and wrote the manuscript; Ling He supervised the review. All authors have read and approved the final version of the manuscript, and agree with the order of presentation of the authors.

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He, L., Sun, Y. The potential role of Keap1-Nrf2 pathway in the pathogenesis of Alzheimer’s disease, type 2 diabetes, and type 2 diabetes-related Alzheimer’s disease. Metab Brain Dis (2021). https://doi.org/10.1007/s11011-021-00762-z

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Keywords

  • Alzheimer’s disease
  • Diabetes mellitus
  • Oxidative stress
  • Keap1-Nrf2 signaling pathway
  • Antioxidant agents