A Concise Review on Oxidative Stress-Mediated Ferroptosis and Cuproptosis in Alzheimer's Disease

Alzheimer's disease (AD), which was first identified more than a century ago, has become a pandemic that exacts enormous social burden and economic tolls as no measure of combating devastated AD is currently available. Growing etiopathological, genetic, and biochemical data indicate that AD is a heterogeneous, polygenic, multifactorial, and complex disease. However, its exact etiopathology remains to be determined. Numerous experimental data show that cerebral iron and copper dyshomeostasis contribute to A beta amyloidosis and tauopathy, two neuropathological hallmarks of AD. Moreover, increasing experimental evidence suggests ferroptosis, an iron-dependent and nonapoptotic form of cell death, may be involved in the neurodegenerative process in the AD brain. Thus, the anti-ferroptosis approach may be an efficacious therapeutic strategy for AD patients. Furthermore, it remains to be further determined whether cuproptosis, a copper-dependent and distinct form of regulated cell death, also plays a contributing role in AD neurodegeneration. We hope this concise review of recent experimental studies of oxidative stress-mediated ferroptosis and cuproptosis in AD may spur further investigations on this timely and essential line of research.