Ferroptosis Modulators: A Potential Therapeutic Target in Alzheimer’s Disease

Abstract

The most commonly known dementia, i.e., Alzheimer’s disease (AD) occurs in older age people and it is an irreversible neurodegenerative disorder of the brain that is primarily regarded as a decline in thinking and independence in daily activities. It is well documented that the disease development starts the years before the warning signs are evidenced and at that point most treatments become ineffective. Over a long time, vascular risk factors have been connected with cognitive decline and higher risk of AD through increased tau and cerebral amyloid β (Aβ) aggregates. Unlike programmed cell fate to death, ferroptosis is oxidative stress or aggregation of lipid peroxide and iron-reliant cell death associated with AD. The exact mechanism of action of ferroptosis in AD, related pathways, and differentially expressed genes need to be widely investigated. Ferroptosis hallmarks such as high levels of iron level, oxidative stress, and accumulation of lipid peroxides were investigated in the AD brain. Further, it was noticed that the development of neurofibrillary tangles and Aβ plaques are associated with iron burden in AD mice models. Here, we summarize the recent development of a ferroptosis-related molecular mechanisms, and chemical modulators of ferroptosis in order to control the progression of AD progression. The details of the existing potential targets for therapeutics in order to avert the ferroptosis in AD have been discussed. Ferroptosis-related studies for AD treatment in the future might be based on creating novel techniques and therapeutic agents to modulate ferroptosis in AD brain and construct animal models of AD in order to identify ferroptosis modulators to stop or reverse the neurodegeneration in AD. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.