Targeting the Key Neuroinflammatory Pathway in Brain Aging

Project Description

An intriguing feature of biological aging is that different individuals age at a different rate. In the case of brain aging, age-related memory impairment and Alzheimer’s Disease (AD) affect part of the population while spare others. This proposed study seeks to characterize the key gene regulatory programs that drive a healthy aging brain toward pathological changes (such as deposition of senile plaques), especially via age-related neuroinflammation and microglial activation. To achieve this research goal, we have comprehensively combined AAV-based CRISPR perturbation, multi-omic sequencing analysis, molecular pathology and machine-learning based 3D cell image tracking tools. We have already demonstrated the key role of an aging-dependent transcription factor (TF) ATF3 in microglia. We will pursue new IPs with VitaDAO on anti-aging and anti-AD small chemicals based on our small chemical leads (A31 and A32) that target the downstream pathway of ATF3.