Yujun Hou, PhD | Tongji University; Jianhuang Xue, PhD
Competition Sponsor: Chinese Academy of Medical Sciences
Awardee Year: 2024
Alzheimer’s disease (AD), characterized by progressive neurodegeneration, cognitive and memory impairments, and neuronal loss, is a major global health concern in the aging population. Current treatments have limited efficacy in halting AD progression. This project focuses on PL402, a novel compound derived from natural products. Initial tests have demonstrated its potential to improve cognitive function in AD patients. In this project, we will comprehensively evaluate PL402’s effects on AD model mice, including spatial learning and memory, social behavior, locomotor functions, and muscle strength. Moreover, the impacts of PL402 on AD pathologies such as Aβ plaque, neuroinflammation, cellular senescence, and its role in neuronal survival and neurogenesis will be investigated. Mechanistically, the influence of PL402 on gene expression and immune signaling will be analyzed. Previous results showed that PL402 could suppress the cGAS-STING pathway. We aim to clarify how PL402 modulates this pathway to reduce neuroinflammation and achieve therapeutic outcomes. Epigenetic changes in the PL402-treated AD mice have also been observed. Future work will focus on deciphering how these epigenetic changes affect gene expression and AD progression, and exploring whether PL402 can alleviate neuroinflammation by regulating epigenetic modifications, potentially providing a new treatment basis. To ensure clinical applicability, we will conduct pharmacodynamics and toxicological studies to assess the safety and efficacy of PL402 and determine its tissue distribution and toxicity at different doses. The project is expected to provide a potential option for AD treatment and new insights into relevant mechanisms, contributing to an improved prognosis for AD patients.