Uncovering How to Protect Nerves in Neurodegenerative Diseases

Researchers at the Case Western Reserve University School of Medicine have led a team that has discovered a novel therapeutic strategy for treating neurodegenerative illnesses, raising the prospect of better care for conditions like multiple sclerosis, Alzheimer's disease, Parkinson's disease, and Vanishing White Matter disease.

Paul Tesar. Image Credit: Case Western Reserve University

According to the National Institutes of Health, neurodegenerative diseases, which impact millions of people globally, arise when nerve cells in the brain or nervous system eventually stop functioning and die. The two most prevalent diseases are Parkinson’s and Alzheimer’s.

The study team's latest work, released online in the journal Nature Neuroscience, concentrated on astrocytes, the most prevalent type of brain cells that typically support normal brain function. There is mounting evidence that astrocytes in neurodegenerative diseases can transition to a detrimental state that accelerates the loss of nerve cells.

The scientists developed a novel cellular method to assess the potential of thousands of drugs to stop the formation of these rogue astrocytes.

By harnessing the power of high-throughput drug-screening, we’ve identified a key protein regulator that, when inhibited, can prevent the formation of harmful astrocytes.”

Benjamin Clayton, Lead Author and Career Transition Fellow, National Multiple Sclerosis Society, Laboratory of Paul Tesar, Case Western Reserve School of Medicine

They discovered that inhibiting the function of a specific protein, HDAC3 may stop the growth of potentially harmful astrocytes. The researchers found that by giving drugs that specifically target HDAC3, they could significantly improve nerve cell survival in mouse models and stop the growth of potentially harmful astrocytes.

This research establishes a platform for discovering therapies to control diseased astrocytes and highlights the therapeutic potential of regulating astrocyte states to treat neurodegenerative diseases.”

Paul J. Tesar, Study Principal Investigator and Professor, Innovative Therapeutics, Dr Donald and Ruth Weber Goodman, Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine

Tesar, also the Director of the Institute for Glial Sciences at the School of Medicine, stated that additional research is necessary before patients could profit from the intriguing strategy. However, he added, their research may result in the development of novel treatments that neutralize dangerous astrocytes and promote neuroprotection, potentially extending the lives of those who currently suffer from neurodegenerative diseases.

Therapies for neurodegenerative disease typically target the nerve cells directly, but here we asked if fixing the damaging effects of astrocytes could provide therapeutic benefit. Our findings redefine the landscape of neurodegenerative disease treatment and open the door to a new era of astrocyte targeting medicines.”

Paul J. Tesar, Study Principal Investigator and Professor, Innovative Therapeutics, Dr Donald and Ruth Weber Goodman, Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine

Other researchers from the George Washington School of Medicine, Ohio State University, the University of Tampa, and Case Western Reserve School of Medicine were also a part of the team.

Case Western Reserve University

Journal reference:

Clayton, L. L. B., et al. (2024) A phenotypic screening platform for identifying chemical modulators of astrocyte reactivity. Nature Neuroscience. doi.org/10.1038/s41593-024-01580-z.

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