Publication of a New Study on ALS Neurodegeneration in 《Nature Aging》

Throughout human history, numerous mysterious diseases have posed significant challenges for scientific research. Among these, Amyotrophic Lateral Sclerosis (ALS), a progressive neurodegenerative disease, is known for the gradual loss of muscle function and disability it causes. Unfortunately, the battle for the patients’ lifeline often ends within 2 to 5 years after symptom onset. The exploration of ALS causes has long been a crucial field in modern neuroscience research.

Today, in the journey against neurodegenerative diseases, a new research achievement has been presented to the world. In July 2024, the journal 《Nature Aging》 published a research article written by Kevin Eggan and his team. The core of this research lies in single nucleus sequencing technology, which reveals that specific extratelencephalic neurons in ALS patients are particularly sensitive to degenerative changes and exhibit elevated expression of genetic risk factors.

Research Background and Significance

ALS, commonly known as Lou Gehrig’s disease, is characterized by the degeneration and functional loss of specific groups of neurons. Studies have shown that particularly extratelencephalic neurons (ETNs)/Betz cells are most susceptible. However, the mystery of why these neurons are specifically affected remains unsolved. Eggan’s team, in this study, attempts to investigate the unique molecular characteristics that make ETNs particularly sensitive to ALS.

The study collected 79,169 single nuclei from the cortices of patients and control groups. Through RNA sequencing, it was found that in patients, and even in unaffected individuals, genes associated with ALS risk had significantly higher expression in Thy1+ ETNs.

Research Origin and Authors

This research was conducted by Francesco Limone, Daniel A. Mordes, Kevin Eggan, and others from several renowned research institutions. The article was published online on June 21, 2024, and appeared in Volume 4 of the July issue of 《Nature Aging》.

Research Details

a) Research Process:

In this study, researchers used advanced single nucleus RNA sequencing technology to conduct an in-depth molecular analysis of the cortices of ALS patients and control groups.

b) Main Results:

The results showed that the expression of ALS risk genes in Thy1+ ETNs was significantly increased in both ALS patients and healthy individuals. Additionally, genes involved in protein homeostasis and stress response were induced, and these genes were significantly induced in a broad range of ETNs in patients.

c) Research Conclusion and Significance:

The study concludes that the selective susceptibility of ETNs to ALS is partly due to their inherent molecular characteristics, making them more sensitive to genetic and degenerative mechanisms.

d) Research Highlights:

The study’s highlight lies in identifying specific neuron subtypes that serve as disease benchmarks in ALS and elucidating the molecular mechanisms within these cells.

Research Significance and Potential Impact

The susceptibility of ETNs in ALS may provide a foundation for developing more targeted therapeutic strategies. It also holds tremendous scientific value for understanding the mechanisms of the disease, potentially driving advancements in disease modeling, establishing diagnostic standards, and innovating future treatment methods.

Conclusion

Eggan’s team’s research reveals the susceptibility of specific cell subtypes in the brains of ALS patients and paves a new way for exploring therapeutic targets for ALS. In the long history of humanity’s battle against diseases, many precious lives have been lost. In this enduring struggle, each scientific advancement is a brave step towards declaring war on lethal diseases.