Scientists identify genes linked to brain cell loss in ALS

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Friday June 21, 2024

NIH-funded study sheds light on disease mechanism and possible therapeutic targets

A brain tissue sample from a human was used to map the genetics of SOD1, a gene associated with ALS. Researchers discovered higher levels of gene expression (light blue and green) in rare neuron types located deep in the cerebral cortex.Eggan Laboratory, Harvard University.

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Researchers have discovered that a set of genes can cause neurons to die in people with sporadic Alzheimer's disease. Amyotrophic lateral sclerosis. Results published in Nature AgingThe study was funded by the National Institutes of Health (NIH). This could provide new information about the causes of ALS and lead to ways to slow the progression of the disease. The National Institutes of Health funded the study.

ALS, a progressive neurodegenerative disease, attacks the motor neurons in the spinal cord and brain that control muscle movements. This leads to muscle weakness and paralysis. Ultimately, ALS can lead to death. The majority of cases of ALS are sporadic and occur without a clear family history.

Researchers identified genes associated with ALS, FTD, and ALS by analyzing thousands of neurons in postmortem brain tissue from individuals with ALS. These genes are most important in Betz motor neurons, which express the marker. THY1. This was found to be linked to disruptions in other neurons that affect their ability to transport and build proteins. Genes, including SOD1, KIF5A“  CCHHD10“…are the symptoms most commonly associated with ALS/FTD.

Further experiments revealed that the changes could be linked to the accumulation of the toxic protein TDP43. This is a defining characteristic of ALS and, in some cases, FTD. Therefore, increased levels of ALS risk genes within a specific cell type can trigger a chain reaction leading to neuronal loss.

The Betz cell is suspected to be a hallmark of ALS. It is believed to occur early, when symptoms first appear. It is possible to develop new treatments that can slow or even stop the progression of ALS by understanding what makes these and other cells vulnerable.

The team studied how damage to glial cells is caused by ALS. In ALS, glial cells, which normally support neurons and keep them healthy, can damage neurons. This often accelerates their decline. The researchers analyzed the genetic information of two types of glial cells and discovered genes linked to inflammation and cellular stress. More research is needed to determine whether glial cell dysfunction leads to or is a cause of the neuronal degeneration that occurs in ALS.

Taken together, the study results improve our understanding of why certain neurons are more vulnerable to ALS. Identify new therapeutic targets.

This study was funded by the National Institute on Aging and the National Institute of Neurological Disorders and Stroke. The NIA-funded Massachusetts Alzheimer's Disease Research Center (one of 35 research centers in the United States) provided single-cell sequencing and other resources.

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Amélie G. Gubitz Ph.D. is the program director at NINDS and can discuss the study results. For an interview, please contact NINDSPressTeam@ninds.nih.gov.

The article below provides more information about the item.

Limone, F., et al. “A unique core sequence reveals enriched gene expression in an extratelencephalic neuron susceptible to degeneration. » Aging Nature. June 21, 2024. DOI: 10.1038/s43587-024-00640-0.

NINDS NINDS is the leading funding agency for research in the United States on the nervous system and the brain. The mission of NINDS is to gain fundamental knowledge of the nervous system, brain, and other organs and to use this knowledge to alleviate the burden of neurological disease.

The National Institute on AgingNIA is the lead agency of the U.S. federal government responsible for conducting and supporting research related to aging and the health and well-being of older adults. NIA offers a wealth of information on age-related changes in cognition and neurodegenerative diseases. Website of the Education and Reference Center on Alzheimer's Disease and Associated Dementias (ADEAR).. You can find information on a wide range of aging topics on the main NIA website. English You can also learn more about the following topics: Spanish » Stay connected.

The National Institutes of Health: NIH is the American medical research agency of the United States Department of Health and Human Services comprised of 27 institutes and centers. The NIH, the nation's medical research agency, is the primary federal agency that conducts and supports basic, translational, and clinical medical research. , treatment and cures for common and rare diseases. Visit the NIH for more information about its programs and services www.nih.gov

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