Shijun Zhang is an associate professor in the VCU School of Pharmacy's Department of Medicinal Chemistry. (Photo courtesy Allen Jones/VCU)
On the subject of Alzheimer’s disease, Shijun Zhang is thinking small.
Researchers in his Virginia Commonwealth University laboratory are crafting molecules to inhibit inflammation linked to development of Alzheimer’s. Their work in mice has shown a reduction in inflammation and improved cognition skills, and they’ve recently received a $609,403 federal grant to continue the project.
The basis for the research is the concept that neuroinflammation (inflammation of nervous tissue) plays a key role in the development of Alzheimer’s disease. Zhang’s team is focused on one particular multiprotein platform, NLRP3 inflammasome. They’ve developed an inhibitor to block the structure, which activates inflammation.
The hope is that this will lead to development of a medication with small molecule inhibitors that will target the platform and prevent or inhibit disease progression. The researchers report that the inhibitor resulted in reduced pathology and improved cognition in mice used in the study. The preliminary work also showed that their “chemical scaffold” could be improved, a goal for the next phase.
“We do see quite promising results,” Zhang said in a phone interview on Thursday.
About 5 million Americans have Alzheimer's according to the National Institute on Aging, the source of the grant. The disease impacts thinking and memory. It is progressive and irreversible.
Zhang, an associate professor of medicinal chemistry in the School of Pharmacy and a VCU Massey Cancer Center researcher, came to VCU in 2007 after working at the University of Minnesota. His laboratory is also focused on researching the use of hybrids of melatonin and curcumin as protectants against Alzheimer’s, and development of compounds against the disease.
The laboratory in which he worked in Minnesota had focused on opioids, but the skill set translated well to Alzheimer’s disease research, he says. It's an intriguing line of work, one in which only a limited number of medications is currently available, and in which more work is needed to learn about the mechanisms behind its development.
