A research team led by Professor Mi Hee Lim from the Department of Chemistry announced that they have devised new simple principles for designing molecules that react against pathogenic factors in neurodegenerative disorders such as Alzheimer’s disease. The study, published on April 1, was featured in the Journal of the American Chemical Society (JACS) as the ACS Editors’ Choice on May 6.

Reactive oxygen species (ROS) are chemical species containing oxygen. Due to the high reactivity of ROS, their rates of production and removal in reactions must be carefully controlled. An imbalance in these processes results in excess amounts of free radicals, which, in turn, can lead to oxidative stress by causing damage in cells. Several factors contribute to the substantial production of ROS in the brain, such as increased O2 metabolism, excessive amount of metal ion concentration, and deficient antioxidant capacity.  As neurons tend to be particularly vulnerable to oxidative stress, ROS are believed to be responsible for the process of neurodegeneration in Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). also known as motor neurone disease. 

Moreover, the interaction of ROS with amyloid-beta proteins — peptides crucially involved in Alzheimer’s disease — and metal ions further aggravate a patient’s condition and hinders medical treatment of Alzheimer’s disease. Clinical attempts to prevent oxidative stress with natural antioxidants have been unsuccessful; hence, developing a solution that targets several pathogenic factors remains key in treating this disease.

Professor Lim’s research team, in conjunction with the groups of Professor Mu-Hyun Baik and Joo-Young Lee at the Asan Medical Center, demonstrated that aromatic molecules of surprisingly simple structural composition can exhibit multiple beneficial reactivities against these pathogenic factors. The researchers selected ten molecules by adjusting the electronic distribution of certain reaction groups to yield redox-dependent reactivities, which turned out to be crucial to their function as chemical tools against pathogens.

The team performed a test on the brain of a transgenic mice suffering from Alzheimer’s disease using the most promising candidate molecule and observed a significant reduction in cerebral and hippocampal amyloid-beta deposits and improvements in the cognitive function of the mice. 

Professor Lim commented that this strategy is simple and efficient and has the potential to improve the lives of many Alzheimer’s patients.