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Grants > Mitochondrial DNA Damages and Microglia Activation in Alzheimer’s Disease Updated On: Feb. 2, 2025
Alzheimer's Disease Research Grant

Mitochondrial DNA Damages and Microglia Activation in Alzheimer’s Disease

Metabolism & Bioenergetics
a headshot of Dr. Guo

Principal Investigator

Lan Guo, PhD

University of Kansas Center for Research

Lawrence, KS, USA

About the Research Project

Program

Alzheimer's Disease Research

Award Type

Standard

Award Amount

$300,000

Active Dates

July 01, 2022 - June 30, 2025

Grant ID

A2022036S

Goals

The goal of this project is to establish a cause-and-effect link between mitochondrial DNA deregulation and microglial activation in AD mice model.

Summary

Microglia-mediated neuroinflammation contributes to the pathogenesis of Alzheimer’s Disease (AD), the mechanisms of AD-related microglial activation are not fully understood. In view of our preliminary data, we aim to establish a cause-effect relationship of oxidative damage and the subsequent leakage of mitochondrial DNA (mtDNA) with inflammatory microglial response via activation of cytosolic DNA-sensing system in AD-related conditions. Positive results will reveal a novel mitochondrial pathway of neuroinflammation in AD and hold promise to develop innovative therapy for AD treatment.

Unique and Innovative

The proposed proof-of-concept study presents a highly novel approach to address the yet not fully answered question of what mediates early microglial activation in AD. We have raised a novel concept that mtDNA oxidative damages in microglia contribute to microglial activation in AD through mtDNA leakage to cytosol. Our investigation will comprehensively examine this novel mechanism and deepen our understanding of pathogenesis of AD.

Foreseeable Benefits

If our study is complete, it will provide a new avenue for the development of therapeutic strategies by targeting mtDNA oxidative damages and leakage for AD therapy. Because similar brain pathologies occur in other neurodegenerative diseases, the findings from this study will potentially stimulate research into other neurodegenerative diseases, such as Down’s syndrome and Lewy body dementia, which involve brain amyloidopathy and microglial inflammatory activation.