The Potential of Ferroptosis-Targeting Therapies for Alzheimer's Disease: From Mechanism to Transcriptomic Analysis

Alzheimer's disease (AD), the most common form of dementia, currently affects 40-50 million people worldwide. Despite the extensive research into amyloid beta (A beta) deposition and tau protein hyperphosphorylation (p-tau), an effective treatment to stop or slow down the progression of neurodegeneration is missing. Emerging evidence suggests that ferroptosis, an iron-dependent and lipid peroxidation-driven type of programmed cell death, contributes to neurodegeneration in AD. Therefore, how to intervene against ferroptosis in the context of AD has become one of the questions addressed by studies aiming to develop novel therapeutic strategies. However, the underlying molecular mechanism of ferroptosis in AD, when ferroptosis occurs in the disease course, and which ferroptosis-related genes are differentially expressed in AD remains to be established. In this review, we summarize the current knowledge on cell mechanisms involved in ferroptosis, we discuss how these processes relate to AD, and we analyze which ferroptosis-related genes are differentially expressed in AD brain dependant on cell type, disease progression and gender. In addition, we point out the existing targets for therapeutic options to prevent ferroptosis in AD. Future studies should focus on developing new tools able to demonstrate where and when cells undergo ferroptosis in AD brain and build more translatable AD models for identifying anti-ferroptotic agents able to slow down neurodegeneration.

Automated summary

This review summarizes the current knowledge on the cell mechanisms involved in ferroptosis, discusses how these processes are related to AD, and analyzes differentially expressed ferroptosis-related genes in the AD brain based on cell type, disease progression, and gender. Existing targets for therapeutic options to prevent ferroptosis in AD are identified, and future studies should focus on developing new tools to demonstrate when and where cells undergo ferroptosis in the AD brain and establishing more translatable AD models to identify anti-ferroptotic agents that can slow down neurodegeneration.