According to Northwestern Medicine Research, new experimental molecules have great promise in targeting enzymes in the brain that prevent memory loss in Alzheimer’s disease. Developed in D. Martin Watterson’s laboratory, the molecules halted memory loss and were able to fix damaged communication between brain cells in mice.
Researchers identified and targeted a key enzyme: a stress-related protein kinase known as p38pha MAPK, which has been known to over-produce and cause brain inflammation as well as impaired neuron function throughout the course of Alzheimer’s disease. From there the scientists utilized Northwestern’s premier structural genomics capabilities to create the MW108 molecule, designed to act as a drug to reduce the activity of the targeted protein kinase. In the first batch of experiments, mice brains were injected with beta-amyloid proteins to simulate a human brain wrought with Alzheimer’s. One group of mice was given the new drug MW108, while another group was given a placebo. In a series of water maze tests, where mice were led to a platform based on their memory of certain environmental cues, the mice given the MW108 found the resting platform just as quickly as the control group of mice. The placebo group of mice took longer to find the platform and often made mistakes in the process of recalling the environmental cues. These results show that the molecule actively prevented cognitive impairment in the mice. Through a series of additional experiments, Drs. Anderson and Valerie Grum-Tokars were able to develop a three-dimensional structure of human p38 MAPK, enabling further designs and synthesis of new drug-like molecules to disable the enzyme and better treat early to mid-stage Alzheimer’s disease.
1) D. Martin Watterson, Valerie L. Grum-Tokars, Saktimayee M. Roy, James P. Northwestern University (2013, June 26). Promising Alzheimer’s ‘drug’ halts memory Schavocky, Brinda Desai Bradaric, Adam D. Bachstetter, Bin Xing, Edgardo Dimayuga, Faisal Saeed, Hong Zhang, Agnieszka Staniszewski, Jeffrey C. Pelletier, George Minasov, Wayne F. Anderson, Ottavio Arancio, Linda J. Van Eldik. Development of Novel In Vivo Chemical Probes to Address CNS Protein Kinase Involvement in Synaptic Dysfunction.
2) Northwestern University (2013, June 26). Promising Alzheimer’s ‘drug’ halts memoryloss. ScienceDaily. Retrieved June 28, 2013, from http://www.sciencedaily.comreleases/2013/06/130626184019.htm
By Lauren Horne