Captured the ‘Lipid’ That Causes Protein Aggregation... GIST Finds Clues to Inhibiting Parkinson’s Progression [Reading Science]

Ceramide Accumulation Identified as Key Pathological Factor

Neuronal Protection Confirmed in Animal and Patient Models

A new study has found that modulating 'lipid metabolites' that trigger protein aggregation—known to be a cause of Parkinson's disease—can slow the progression of the disease. This achievement demonstrates the possibility of blocking the fundamental pathological pathway of the disease, extending beyond conventional approaches that focus only on symptom relief.

The Gwangju Institute of Science and Technology (GIST) announced that a research team led by Professor Changmyung Oh of the Department of Biomedical Science and Engineering at GIST has identified the accumulation of ceramide—a lipid component within brain cells—as a key driver of protein aggregation and neuronal damage. The team proposed a strategy to mitigate the progression of Parkinson's disease by inhibiting this process.

Recovery Effects of Myriocin on Pathology and Behavior in Parkinson's Disease Mice. An experimental plan involved injecting Myriocin (0.4 mg/kg) three times a week from 5 months of age in a Parkinson's disease model mouse (a). The Myriocin-treated group showed reduced loss of dopamine neurons and alpha-synuclein aggregation (b, c), and improvements in impaired motor function and memory were confirmed through open field and Y-maze tests (d, e). Provided by the research team

The results of this study were published online on January 21 in the international Nature journal 'npj Parkinson's Disease.'

Identifying the 'Lipid to Protein Aggregation' Pathological Pathway

Parkinson's disease is a representative neurodegenerative disorder affecting about 10 million people worldwide. It is characterized by the gradual degeneration of dopamine-producing neurons, leading to symptoms such as tremors and gait disturbances due to impaired motor functions. Current treatments are limited to alleviating symptoms, and there is no therapy that fundamentally halts disease progression.

The research team focused on 'ceramide,' a lipid that constitutes cell membranes and is involved in cell signaling. Ceramide is abnormally accumulated in aging and neurodegenerative diseases and is known to promote the aggregation of alpha-synuclein protein in Parkinson's disease.

In fact, analysis of brain tissue from patients with Lewy body dementia revealed an increase in 19 types of ceramide compared to normal, and elevated activity of genes related to the enzymes (such as CERS5 and CERS6) responsible for their synthesis.

Functional Improvement Confirmed in Animal and Patient Models

The research team then verified the effects of ceramide inhibition using animal models and patient-derived cells.

When the Parkinson's disease model mice were administered 'Myriosin,' a substance that inhibits ceramide synthesis, over a prolonged period, the results showed reduced protein aggregation, improvements in motor function and memory, and decreased damage to dopamine neurons.

The same effects were observed in midbrain organoids and neurons derived from patient stem cells. Conversely, when ceramide was added, protein aggregation and neuronal damage increased again, confirming that this substance is directly involved in the pathological process.

Photo of the research team. From the left, Changmyung Oh, Professor of Biomedical Engineering at GIST, and Dr. Eunkyung Lee. Courtesy of GIST

The research team also found that ceramide inhibition activates the removal of damaged mitochondria (mitophagy) and reduces neuroinflammation and cell death.

Professor Changmyung Oh of the Department of Biomedical Science and Engineering at GIST stated, "This study demonstrates the possibility of blocking the fundamental disease pathway leading from protein aggregation to neuronal death, moving beyond simple symptom relief. We plan to continue our work by developing safe inhibitors and conducting long-term toxicity tests for future clinical applications."

GIST plans to promote technology transfer, seeing high potential for industrial application of these findings, including drug development.

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