GSK-3 seminar at Hong Kong University

Today, I accompanied the Onwon Trading Co. team to a seminar for researchers at the Research Centre of Heart, Brain, Hormone, and Healthy Aging of Hong Kong University.  The talk was given by Chandra Mohan, PhD of Merck Biosciences on the topic “Glycogen Synthase Kinase-3: Its Signaling Role in Development and Disease.”

To facilitate research and provide training opportunities, the Heart, Brain, Hormone & Healthy Aging Laboratory has been set up on the 5th Floor of the Laboratory Block, Faculty of Medicine Building, under the supervision of a laboratory committee, consisting of a Deputy Director and 3 Investigators.

After extensive consultation of Centre investigators, it was decided that the following 3 core facilities for Healthy Aging Research should be established within the Centre Laboratory.

1. Functional genomics: this will include facilities and expertise for understanding the gene function and dysfunction in aging-related diseases by making use of transgenic/knock-out mouse models generated by conventional and conditional approaches, siRNA (in vitro and in vivo), and global gene and protein expression (microarray and proteomics).
2. Biomarkers & phenotying: this will include the multiplex assays for inflammatory, oxidative and hormonal changes, as well as metabolic, haemodynamic and behavioral assessments.
3. Cell and tissue engineering: this will include human and mouse stem cell culture & differentiation, and recombinant viral vector generation.

Now, some highlights of Dr. Mohan’s talk on GSK-3.

Abnormalities in pathways that use GSK-3 as a regulator have been linked to several disease conditions. Hence, GSK-3 has emerged as a potential therapeutic target, particularly in non-insulin-dependent diabetes mellitus, Alzheimer’s disease, developmental disorders, and cancer. Several new GSK-3 inhibitors have recently been developed, most of which act in an ATP competitive manner. Inhibitors belonging to aloisines, the paullones, and the maleimide families have shown promise as therapeutic agents. Due to its involvement in multiple pathways, selectivity of GSK-3 inhibition is an important factor in the development of inhibitors for therapeutic applications.

“As we see people living longer,” said Dr. Mohan, “we see more and more dementia, which includes a loss of memory and loss of cognitive function.”

Alzheimer’s disease attacks specific neurons—the ones in areas of the brain that govern memory and cognitive capabilities. “What causes the loss of neurons is a fascinating field of research,” says Mohan. So far, scientists know of two processes involved in Alzheimer’s disease. For one thing, β:-amyloid proteins—just 40-42 amino acids long—get deposited between neurons in specific areas of the brain. Mohan says, “These peptides slow down the function of neurons and produce free radicals that lead to cell death.” In addition, too much phosphorylation of tau proteins destroys the function of microtubules, which inhibits intracellular processes, such as transporting mitochondria throughout a cell. Neurons die when they include overly phosphorylated tau proteins, which also arises in Alzheimer’s disease. “We have tried to concentrate on product lines in both these areas,” says Mohan. For example, Merck Biosciences carries a line of GSK-3 inhibitors. The GSK-3 enzyme causes phosphorylation. Mohan says, “GSK-3 is the most important enzyme. It is the most widely studied right now.”

Merck Biosciences carries antibodies against tau phosphorylation at specific amino acids: serine, threonine, and tyrosine.  You can take a brain section, use immunohistochemistry, and see where the phosphorylated tau was located.

Chandra Mohan received his PhD in 1976 from Bangalore University and did his post-doctoral work from 1977 to 1983 at the University of Southern California, School of Medicine.  From 1983 to 1993 he was an Assistant Professor of Pharmacology and Nutrition at the University of Southern California, Medical School in Los Angeles.  During this time he also served as an Associate Editor of the journal “Biochemical Medicine and Metabolic Biology.”  He joined Calbiochem (now EMD/Merck) in 1993 and is currently the Senior Director of Technical Services and Senior Technical Writer. His research interests include diabetes, biochemical basis of stress, inflammation, and the biology of aging.

After the seminar, our friends from Onwon (Geoffrey, Peter, Nelson and Frankie) had good discussions and follow-up with the researchers who attended.