Alzheimer's disease is the sixth leading cause of death in the United States, and the number of patients with the disease is set to hit 20 million by 2050. In addition, necroptosis is a form of cell death that is found to occur in virtually all tissues. Its key feature is the disruption of the cell membrane that results in an inflammatory immune response. This study aimed to investigate the role of necroptosis in the development of Alzheimer's disease through a literature review. It was found that necroptosis not only occurs in Alzheimer's disease but also may play a crucial role due to several factors. Hyperglycemia activates the switch from apoptosis to necroptosis, and Alzheimer's disease is considered "diabetes type 3.' Second, reactive oxygen species are produced in excess during necroptosis, and affect the production of amyloid beta in Alzheimer's. Inflammation, a key consequence of necroptosis, also increases neurodegeneration and contributes to the overproduction of amyloid beta. These connections lend themselves to the 'starving brain' theory of Alzheimer's disease, and insulin resistance exacerbates the role of necroptosis in the development of Alzheimer's disease. Necroptosis may have a vicious-cycle effect in Alzheimer's disease due to various factors, and it is a key therapeutic target in Alzheimer's disease that should be further examined.
Keywords: Alzheimer’s disease; Cell death; Dementia; Hyperglycemia; Insulin resistance; Necroptosis; Neuroinflammation; Reactive oxygen species.
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