Suppressing Brain Immune Cell Inflammation to Treat ALS…Brain Research Institute Discovers Natural Candidate Substance [Reading Science]

A New Therapeutic Strategy Targeting Astrocytes

Simultaneous Approach for ALS and Frontotemporal Dementia

Effectiveness Confirmed in Cells, Animal Models, and Patient Blood

Spotlight on the Natural Product-Derived Candidate Compound 'DHE'

A team of Korean researchers has proposed a new therapeutic strategy to suppress excessive inflammatory responses in brain immune cells that exacerbate amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). By confirming the therapeutic potential of a candidate substance derived from natural products in cells, animals, and patient blood, the research has opened up new possibilities for developing treatments for intractable degenerative brain diseases.

On August 3, the Brain Research Institute of Korea announced that the research team led by Dr. Kim Hyungjun of the Dementia Research Group has clarified the efficacy of the natural product-derived candidate 'dehydrocostus lactone (DHE)', which regulates excessive inflammatory responses in astrocytes to protect neurons.

Therapeutic Strategy Targeting Astrocytes in ALS FTD Using DHE. Courtesy of Brain Research Institute

ALS and frontotemporal dementia are representative degenerative brain diseases that cause loss of motor function and cognitive/behavioral disorders, respectively. Currently, there are no drugs that can fundamentally halt disease progression, and most research to date has focused on directly protecting neurons.

The research team focused on astrocytes, which have recently been highlighted as a major factor aggravating these diseases. Astrocytes normally protect neurons, but once an excessive inflammatory response occurs, they are known to damage neurons instead.

The study found that DHE suppresses the pro-inflammatory 'NF-κB' signaling pathway while activating the antioxidant defense pathway, 'NRF2', thereby effectively reducing excessive inflammatory responses in astrocytes. As a result, the secretion of inflammatory substances decreased, and mitochondrial function in neurons was restored, demonstrating neuroprotective effects.

Therapeutic Potential Confirmed in Cells, Animal Models, and Patient Blood

The research team verified the therapeutic effects through various preclinical stages, including experiments on cells, animal models, and actual patient blood analyses.

In cells derived from ALS patients, there was a significant decrease in the abnormally accumulated FUS protein, and in Drosophila models mimicking ALS and frontotemporal dementia, there was improvement in motor function and extension of lifespan.

Furthermore, they identified increases in inflammatory chemokines in the blood of actual ALS patients, while treatment with DHE significantly reduced these inflammation markers in a mouse astrocyte disease model.

The research team explained that this study is significant because it presents astrocyte-induced neuroinflammation as a new therapeutic target for ALS and frontotemporal dementia, and comprehensively demonstrates therapeutic potential across various preclinical models.

Dr. Kim Hyungjun of the Brain Research Institute of Korea said, "We have confirmed that excessive inflammatory responses of astrocytes play a crucial role in the progression of these diseases, and we demonstrated that controlling these responses can effectively protect neurons. We plan to continue research so that this can eventually lead to the development of actual therapeutics through follow-up studies."

This research was supported by the Ministry of Science and ICT and the National Research Foundation of Korea, and the results were published in the latest issue of the international journal 'Cell Communication and Signaling'.

This content was produced with the assistance of AI translation services.