A joint research team led by Prof. Il Min KWON of SKKU School of Medicine and Prof. Steven L. Mcknight of the University of Texas Southwestern Medical Center, discovered the intercellular targets of toxic PR Poly-dipeptides encoded by C9orf72 repeat expansion which is frequently found in amyotrophic lateral sclerosis (ALS) (also known as Lou Gehrig’s disease). The result of the study may offer a unified means of considering mechanisms of pathogenicity for a broad spectrum of neurodegenerative diseases.

Amyotrophic Lateral Sclerosis (ALS) is a specific disease that causes the death of motor neurons which control voluntary muscles. ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size which results in difficulty speaking, swallowing, and eventually breathing. According to the ALS Association, approximately 350,000 patients (2500 in Korea) are suffering from the disease and about 100,000 people die per year. Although there is not yet a cure or treatment that halts or reverses ALS, scientists have made significant progress in learning more about this disease. Several research projects which were revealed to the public in 2011 have proved that the variation of cell C9orf72 is the main reason for ALS disease occurring.

In this research, two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide, encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding and that interaction between the PRn poly-dipeptide and LC domains is polymerdependent. These studies indicate that PRn-mediated toxicity may result from broad impediments to the dynamics of cell structure and information flow from gene, to message, to protein.

Please refer to the attached article for more information about the research.