[LAB Search] Path Opened for Treatment of Huntington's, Alzheimer's, and Parkinson's Diseases

DGIST Identifies ClpB Function for the First Time
Removes Toxic Protein Aggregates in the Brain
Restores Damaged Neural Functions

A research team at Daegu Gyeongbuk Institute of Science and Technology (DGIST) has discovered clues that could potentially unravel already-formed toxic protein aggregates in Huntington's disease.

From the left, Professor Jae-won Ko, Professor Ji-won Eom, Postdoctoral Researcher Hyunho Kim. DGIST

On December 5, DGIST announced that the research team led by Professors Ji-won Eom and Jae-won Ko from the Department of Brain Sciences has, for the first time in the world, identified the function of the mitochondrial protein 'ClpB,' which directly dissolves and eliminates toxic protein aggregates that play a key role in the onset of Huntington's disease. This finding demonstrates that it is possible to remove protein clumps already accumulated in the brain and even restore damaged neural functions.

Huntington's disease is a rare degenerative brain disorder that is inherited with a 50% probability if one parent is a carrier. Symptoms such as memory loss, abnormal movements, and emotional regulation disorders gradually appear. Although the cause of the disease is relatively well understood, there are no drugs that can reverse or halt its progression, and previous research has been limited to 'preventive strategies' that aim to slow down or block protein aggregation. In particular, the mechanism for completely dissolving already-formed toxic aggregates within the body had not been identified until now.

The DGIST research team focused on the mitochondrial protein ClpB, which operates under stress conditions when proteins become entangled. By precisely controlling the expression of ClpB in Huntington's disease cell models and mice, the team found that when ClpB levels were insufficient, even normal proteins aggregated easily and neural damage increased. Conversely, increasing ClpB levels led to a noticeable reduction in mutant huntingtin protein aggregates.

This discovery is significant because it could be extended to treatment strategies for various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), where protein aggregation is a major pathological mechanism. The research team was the first to prove that ClpB functions as a protein disaggregase, operating not at the prevention stage but at the repair and disassembly stage, and they expect it could become a new drug target.

Professor Eom stated, "This study is highly meaningful as it confirms the actual existence of a mechanism that can directly dissolve toxic protein clumps already accumulated in the brain. It goes beyond simply preventing protein aggregation and presents a new therapeutic direction for restoring already damaged neural functions."

Postdoctoral Researcher Hyunho Kim participated as the first author of this study. The research results were published in the international journal 'Theranostics' in the field of translational medicine. The study was supported by the Ministry of Science and ICT and the National Research Foundation of Korea through the Global Leader Research Program, Mid-career Researcher Program, Basic Research Laboratory Program, and Sejong Science Fellowship.