Research progress of ferroptosis in Alzheimer disease
Research progress of ferroptosis in Alzheimer disease
What's this about?
This article discusses the relationship between a unique type of cell death, "ferroptosis," and Alzheimer's disease (AD) - a neurodegenerative disorder affecting memory and cognition.
What is Ferroptosis?
Ferroptosis is a distinct form of cell death characterized by an overload of iron and reactive oxygen species within the cell. This process results in cellular shrinkage and mitochondrial densification.
How does this relate to Alzheimer's Disease?
Alzheimer's disease leads to neuronal damage, manifesting as memory deficits and cognitive decline. Recent research suggests a potential link between ferroptosis and AD pathology. Elevated ferroptosis-related gene expression has been observed in AD patients, indicating that understanding ferroptosis could provide insights into AD's etiology and potential therapeutic avenues.
What's the big idea?
This article offers a comprehensive review of the current research on the potential connection between ferroptosis and Alzheimer's. It's a promising research avenue that could illuminate novel therapeutic strategies for this debilitating disease.
Understanding Ferroptosis and Its Role in Cells
How does Iron Affect Ferroptosis?
Iron plays a pivotal role in cellular functions. However, excessive intracellular iron can lead to the production of reactive oxygen species (ROS), promoting ferroptosis. Certain proteins, like "heat shock protein β1," can regulate intracellular iron levels, thereby modulating ferroptosis.
What's the Deal with Fats and Ferroptosis?
Polyunsaturated fatty acids (PUFAs) within cells can undergo lipid peroxidation, facilitating ferroptosis. ROS, especially in the presence of elevated iron, can expedite this process.
How do Amino Acids Play a Part?
Amino acids, particularly GSH, play a protective role against cellular damage. GSH, derived from cysteine, acts as a cellular shield against oxidative damage, preventing ferroptosis.
How Ferroptosis Connects to Alzheimer's Disease and Possible Treatments
How Amino Acids Protect Our Brain:
GSH, an amino acid, acts as a cellular defense mechanism, preventing ROS-induced damage. A decline in GSH levels in specific brain regions can be indicative of early Alzheimer's onset.
Iron's Role in Alzheimer's:
Elevated brain iron levels have been associated with AD. Excess iron can induce neuronal damage through ferroptosis and contribute to the formation of Aβ plaques, a hallmark of AD.
How Fats Connect to Alzheimer's:
Brain lipids can undergo peroxidation, leading to neuronal damage and ferroptosis. The Aβ protein, associated with AD, can exacerbate this lipid damage.
Finding Treatments Based on Ferroptosis:
Research is underway to develop treatments targeting ferroptosis to combat AD. Strategies include iron chelation, modulating lipid metabolism, and enhancing GSH levels in the brain.
More Ways to Protect the Brain and Future Hopes for Alzheimer's Treatment
Natural compounds, like Ginkgolide B and salidroside, have shown promise in enhancing brain resilience against ferroptosis. Additionally, understanding the role of cysteine and the system XC− can offer insights into brain protection and cognitive preservation.
Author Contributions:
- Qi Han: Managed the study's data.
- Li Sun: Oversaw the methodology and project management.
- Qi Han & Ke Xiang: Contributed to manuscript review and editing.
Key References:
- Scheltens P, et al. A study on Alzheimer’s disease. Lancet. 2021;397:1577–90.
- Pleen J, Townley R. An update on Alzheimer’s disease clinical trials from 2019 to 2021. J Neurol. 2022;269:1038–51.
- ... (and so on for the other references)