Iron and Alzheimer’s Disease: From Pathogenesis to Therapeutic Implications

As people age, iron deposits in different areas of the brain may impair normal cognitive function and behavior. Abnormal iron metabolism generates hydroxyl radicals through the Fenton reaction, triggers oxidative stress reactions, damages cell lipids, protein and DNA structure and function, and ultimately leads to cell death. There is an imbalance in iron homeostasis in Alzheimer’s disease (AD). Excessive iron contributes to the deposition of β-amyloid and the formation of neurofibrillary tangles, which in turn, promotes the development of AD. Therefore, iron-targeted therapeutic strategies have become a new direction. Iron chelators, such as desferoxamine, deferiprone, deferasirox, and clioquinol, have received a great deal of attention and have obtained good results in scientific experiments and some clinical trials. Given the limitations and side effects of the long-term application of traditional iron chelators, alpha-lipoic acid and lactoferrin, as self-synthesized naturally small molecules, have shown very intriguing biological activities in blocking Aβ-aggregation, tauopathy and neuronal damage. Despite a lack of evidence for any clinical benefits, the conjecture that therapeutic chelation, with a special focus on iron ions, is a valuable approach for treating AD remains widespread.