Study of the Week: Study Reveals a Key Mechanism of Neurodegenerative Diseases

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.


This week’s study is…

Neurotoxic reactive astrocytes induce cell death via saturated lipids

We previously published about this research in a story titled “Scientists Announce Breakthrough Discovery for Alzheimer’s and Other Neurological Diseases,” which can be found here. The study was originally published in the scientific research journal Nature. You can view the abstract of the study here.

This research team was affiliated with New York University.

What Happened?

The medical field continues to struggle in the treatment of neurodegenerative illness. Examples include a wide variety of rare disorders as well as some that are more widespread, such as Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. While some of these illnesses have treatments that can help control symptoms or slow progression, others have almost no effective interventions at all. Without cures, many patients are doomed to lose much of their functional ability. However, the findings from this study have revealed a critical puzzle piece that could help lead to better treatments.

In many neurodegenerative disorders, the neurons, critical cells of the nervous system, begin to die in large numbers. Prior research has suggested that other cells in the brain, called astrocytes, could be involved in this process. Astrocytes are star shaped cells that, when functioning normally, perform important roles, such as regulating the response of the central nervous system towards injuries or disease. They also can clear away toxins in the brain, which normally benefits the function of neurons.

Lab tests using mice revealed that these cells will also destroy neurons that have been damaged. This occurs when the astrocytes release fatty acids with toxic properties. These fatty acids appear to play a decisive role in the death of neurons in neurodegenerative diseases. The scientists identified two fatty acids (saturated lipids contained in APOE and APOJ lipoparticles) as the likely culprit.

In a model of mice with brain damage, the researchers genetically altered half of them to shut down the release of long-chain saturated free fatty acids and phosphatidylcholines. When compared to a control group, these mice saw 75 percent survival of their neurons compared to just 10 percent survival of the controls.

Why Does it Matter?

‘Our findings show the toxic fatty acids produced by astrocytes play a critical role in brain cell death.’ – Professor Shane Liddelow, lead researcher

These results seem to clearly illustrate that A1 astrocytes, which in prior studies have been found to be prevalent in neurodegenerative illnesses like multiple sclerosis, Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease, are responsible for the large scale destruction of neurons and oligodendrocytes that occurs in these illnesses. These findings have the potential to radically alter the understanding of these disease mechanisms.

In addition, this new understanding gives researchers a new approach to treating these diseases. As many neurodegenerative diseases can only be managed with limited effectiveness at best, an approach based on this research could lead to real progress in treatment. The methods used on the mice in this study are not ready for use on human beings, however. Continued research will be needed before it will be possible for a therapy that intervenes in this mechanism to be fully developed.

Neurodegenerative disorders represent one of the greatest medical challenges, and as the human population continues to age, the scientific community has projected that their prevalence is expected to increase in the coming decades. Developing more effective therapies based on breakthrough research like this will be critical to meeting that challenge and ensuring that the patients of the future will have a chance to enjoy a greater quality of life than their predecessors.

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