Research progress of ferroptosis in Alzheimer disease

Ferroptosis and Alzheimer's Disease: A Closer Look

What's this about?

This article talks about the connection between a special type of cell death called "ferroptosis" and Alzheimer's disease (AD). Alzheimer's is a brain disease that affects memory and thinking, mainly in older people.

What is Ferroptosis?

Ferroptosis is a way cells can die, different from other ways we already know. It happens when there's too much iron and harmful oxygen molecules inside the cell. This kind of cell death is unique because the cell's size decreases and parts of the cell called mitochondria become denser.

How does this relate to Alzheimer's Disease?

Alzheimer's disease damages brain cells, leading to memory loss and other problems. Scientists are trying to figure out why this happens. Some recent studies suggest that ferroptosis might play a role in this damage. They found that genes related to ferroptosis are more active in people with Alzheimer's. This means that understanding ferroptosis could help us learn more about Alzheimer's and maybe find better treatments.

What's the big idea?

This article reviews the latest research on how ferroptosis might be linked to Alzheimer's. It's an exciting area of study that could help us better understand and treat this challenging disease.

Understanding Ferroptosis and Its Role in Cells

How does Iron Affect Ferroptosis?

Iron is important in our body. Usually, it travels in our blood and enters cells. But if there's too much iron in a cell, it can cause a reaction that makes harmful molecules called ROS. These molecules can damage the cell and start ferroptosis. Some proteins and genes in our body can control this process. For example, a protein called "heat shock protein β1" can help stop ferroptosis by controlling the amount of iron in cells.

What's the Deal with Fats and Ferroptosis?

Certain fats in our cells can react and cause ferroptosis. These fats, called PUFAs, can change and damage the cell. There's an enzyme that plays a big role in this process. Also, there's a natural substance in our body called α-tocopherol that can stop this damage. Another thing to note is that ROS, those harmful molecules we talked about earlier, are also involved here. They can speed up ferroptosis, especially when there's too much iron in the cell.

How do Amino Acids Play a Part?

Amino acids are building blocks of proteins. One important amino acid is GSH. It's like a superhero for our cells because it protects them from damage. GSH is made from another amino acid called cysteine. If there's not enough GSH, the cell can get damaged and ferroptosis can start.

In Short:

Ferroptosis is a way cells die, and it's linked to iron, certain fats, and amino acids in our body. Understanding this can help scientists learn more about diseases and how to treat them.

How Ferroptosis Connects to Alzheimer's Disease and Possible Treatments

How Amino Acids Protect Our Brain:

Amino acids are like the building blocks of our body. One of them, called GSH, is like a shield for our cells. It stops harmful molecules, ROS, from damaging our cells. If we don't have enough GSH, our cells can get hurt and start ferroptosis. This can lead to brain diseases like Alzheimer's. Some studies have shown that when GSH is low in certain parts of the brain, it can be a sign of early Alzheimer's.

Iron's Role in Alzheimer's:

Iron is important for our brain to work right. But if there's too much iron in the brain, it can cause problems. People with Alzheimer's have more iron in certain parts of their brain. This extra iron can damage brain cells and start ferroptosis. Some studies have shown that iron can also make harmful clumps in the brain, called Aβ plaques, which are linked to Alzheimer's.

How Fats Connect to Alzheimer's:

Our brain has a lot of fats. Some of these fats can change and damage brain cells, leading to ferroptosis. In Alzheimer's, there's a protein called Aβ that can mess with these fats. This can lead to more damage in the brain. Some other studies have shown that certain fats can also affect another protein in the brain, called Tau, which is also linked to Alzheimer's.

Finding Treatments Based on Ferroptosis:

Scientists are looking for ways to treat Alzheimer's by focusing on ferroptosis. Here are some ideas they're exploring:

1. Using Iron Chelators: These are drugs that can remove extra iron from the brain. Some studies have tried this, but the results are mixed. Some patients had side effects.
2. Targeting Fats in the Brain: Some new drugs can stop the bad changes in fats that lead to ferroptosis. These drugs might help treat Alzheimer's. For example, a drug called CMS121 can fix some of the damage caused by Aβ. Another idea is to use Vitamin E, which can slow down Alzheimer's in some patients.
3. Boosting GSH in the Brain: Some drugs can increase the amount of GSH in the brain. This can stop ferroptosis and help repair damaged brain cells. Some studies have shown that these drugs can help in models of Alzheimer's.

In Short:

Ferroptosis is a way brain cells can die, and it's linked to Alzheimer's. By understanding this process, scientists are finding new ways to treat the disease.

More Ways to Protect the Brain and Future Hopes for Alzheimer's Treatment

Using Natural Substances to Boost Brain Protection:

There are some natural substances, like Ginkgolide B and salidroside, that can help protect our brain. They work by increasing the amount of GPX4, which is like a shield for our brain cells. This can stop harmful molecules from damaging our brain and help keep our brain healthy.

How Cysteine Helps Our Brain:

Cysteine is another building block for our body. It helps make GSH, which protects our brain cells. If we don't have enough cysteine, our GSH levels can drop, and our brain cells can get hurt. But, there's a system in our body, called system XC, that can help. If this system is working right, it can stop too much glutamate (another molecule) from hurting our brain. This can protect our brain from damage and keep our thinking sharp.

Looking Ahead - The Future of Alzheimer's Research:

Alzheimer's disease is complicated. Scientists are still trying to figure out all the ways it affects our brain. Right now, there aren't many good treatments for it. But, there's a new idea called ferroptosis that might help. It's a way that cells can die, and it's linked to Alzheimer's. In the future, scientists want to study how ferroptosis connects to our immune system. This might help us understand Alzheimer's better. There are also some genes in the brain that might be important for ferroptosis. If scientists can learn more about these genes, they might find new ways to treat Alzheimer's. Some drugs that stop ferroptosis have already been tested and look promising. But, more research is needed. The hope is that by understanding ferroptosis and other parts of Alzheimer's, scientists can find better treatments and maybe even prevent the disease.

Author Contributions:

• Qi Han: Managed the data for the study.
• Li Sun: Designed the methods and managed the project.
• Qi Han & Ke Xiang: Reviewed and edited the writing.

Key References:

For a deeper dive into the sources, please refer to the original paper. Here are some of the most important references:

1. Scheltens P, et al. (2021) - A study on Alzheimer’s disease. Lancet. 2021;397:1577–90.
2. Pleen J, Townley R. (2022) - An update on Alzheimer’s disease clinical trials from 2019 to 2021. J Neurol. 2022;269:1038–51.
3. Trejo-Lopez JA, et al. (2022) - A deep dive into the brain changes in Alzheimer’s disease. Neurotherapeutics. 2022;19:173–85.
4. Dixon SJ, et al. (2012) - Introduction to ferroptosis: a type of cell death related to iron. Cell. 2012;149:1060–72.
5. Mou Y, et al. (2019) - Ferroptosis in cancer: opportunities and challenges. J Hematol Oncol. 2019;12:34.
6. Huang L, et al. (2020) - How toxic amyloid in cells can lead to a type of cell death called ferroptosis. Cell Death Dis. 2020;11:828.
7. Bao WD, et al. (2021) - The role of iron in memory problems in Alzheimer’s disease. Cell Death Differ. 2021;28:1548–62.
8. Hirschhorn T, Stockwell BR. (2019) - The development of the ferroptosis concept. Free Radic Biol Med. 2019;133:130–43.
9. Shao L, et al. (2021) - How Ginkgolide B can help protect against cognitive problems in mice. Biochem Biophys Res Commun. 2021;572:7–14.
10. Okada M, et al. (2019) - How a drug called Memantine can protect against too much glutamate in the brain. Pharmacol Res Perspect. 2019;7:e00457.

Note: The links provided are general links to the journal websites and may not directly lead to the specific articles.

External Links

Source URL