Copper metabolism and cuproptosis in Alzheimer's disease: mechanisms and therapeutic potential

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder with an increasing incidence rate year by year. The pathogenesis of AD is complex and closely related to protein misfolding and aggregation, neuroinflammation, oxidative stress, mitochondrial dysfunction, and other factors. Cuproptosis is a newly discovered form of programmed cell death caused by excessive intracellular copper. Unlike other known forms of cell death, it shows significant potential in the treatment of neurodegenerative diseases. Copper binds to the acylated components of the tricarboxylic acid cycle, causing protein toxicity stress, which ultimately leads to cell cuproptosis. AD is characterized by pathological features such as β-amyloid plaque formation and excessive phosphorylation of tau protein, which are closely linked to the cuproptosis mechanism. However, the specific relationship between the pathogenesis of AD and copper metabolism remains unclear. This article summarizes the metabolism of copper in the brain, the mechanisms of cuproptosis, and the pathogenesis of cuproptosis in AD, and also discusses the regulation of cuproptosis in the treatment of AD. This article provides a basis for targeted research on cuproptosis in AD.