2017-2018 Alzheimer’s and Related Diseases Research Award*

Development of NLRP3 Inflammation Inhibitors for AD

VCoA*The Virginia Center on Aging which administers the Alzheimer’s and Related Diseases Research Award Fund for the Commonwealth of Virginia, provides seed money to researchers in Virginia to stimulate innovative research into biomedical and psychosocial aspects of dementia, including cell biology, caregiving, and animal modeling.

Development of NLRP3 Inflammation Inhibitors for AD

Shijun Zhang, PhD

Virginia Commonwealth University

Neuroinflammation has been recognized as an essential player in the pathogenesis of AD, especially for the late-onset AD. Inflammasomes have been recently identified as multi protein complexes that tightly regulate the innate immune response and the production of pro-inflammatory cytokines, and the NLRP3 inflammasome is the most extensively studied and widely implicated.  The NLRP3 inflammasome regulates the production of interleukins (IL-1ß and IL-18) and has been indicated as having a critical role in the pathogenesis of AD. The investigator recently developed small molecule NLRP3 inhibitors and one lead compound was identified with in vivo efficacy to reduce AD pathology and to improve memory functions.  The goal of this study is to develop more potent analogs based on the newly identified lead structure.  The results will significantly facilitate development of more potent inflammasome inhibitors as potential disease-modifying agents for AD.

(Dr. Zhang may be contacted at 804/628-8266, szhang2@vcu.edu)


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