Roles of Senescent Microglia in Neurodegenerative Diseases
Our lab is dedicated to understanding the impact of senescent microglia on Alzheimer’s disease (AD) and Parkinson’s disease (PD) using genetic mouse models and cell culture systems. Aging, the primary risk factor for these neurodegenerative diseases, results in the accumulation of senescent cells in the brain. These cells, often referred to as “zombie” cells, are characterized by irreversible cell cycle arrest and distinct phenotypic changes, including increased levels of cell-cycle inhibitors, heightened senescence-associated β-galactosidase activity, and the senescence-associated secretory phenotype (SASP). These cells can persist in tissues and chronically damage their environment through pro-inflammatory factors, potentially leading to the loss of neuroprotective functions and increased brain inflammation. Our research objectives include:
1. Determining how disease conditions promote microglial senescence
2. Identifying the mechanisms that link senescent microglia to neurotoxicity
3. Examining the influence of genetic risk factors on these pathways
We aim to uncover critical insights into microglial senescence and its implications for neurodegenerative diseases by employing reporter mouse lines to detect senescent cells in AD and PD models. This research could potentially reveal new therapeutic targets and enhance our understanding of age-related neurological disorders.