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Review
. 2020 Jan;53(1):35-46.
doi: 10.5483/BMBRep.2020.53.1.274.

Emerging Perspectives on Mitochondrial Dysfunction and Inflammation in Alzheimer's Disease

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Free PMC article
Review

Emerging Perspectives on Mitochondrial Dysfunction and Inflammation in Alzheimer's Disease

Seung-Min Yoo et al. BMB Rep. .
Free PMC article

Abstract

Despite enduring diverse insults, mitochondria maintain normal functions through mitochondrial quality control. However, the failure of mitochondrial quality control resulting from excess damage and mechanical defects causes mitochondrial dysfunction, leading to various human diseases. Recent studies have reported that mitochondrial defects are found in Alzheimer's disease (AD) and worsen AD symptoms. In AD pathogenesis, mitochondrial dysfunction-driven generation of reactive oxygen species (ROS) and their contribution to neuronal damage has been widely studied. In contrast, studies on mitochondrial dysfunction-associated inflammatory responses have been relatively scarce. Moreover, ROS produced upon failure of mitochondrial quality control may be linked to the inflammatory response and influence the progression of AD. Thus, this review will focus on inflammatory pathways that are associated with and initiated through defective mitochondria and will summarize recent progress on the role of mitochondria-mediated inflammation in AD. We will also discuss how reducing mitochondrial dysfunction-mediated inflammation could affect AD. [BMB Reports 2020; 53(1): 35-46].

Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflicting interests.

Figures

Fig. 1
Fig. 1
Mitochondria as a regulator of inflammation. (Upper) Leakage of mitochondrial components. (a) Leaked N-formyl peptide binds to formyl peptide receptor (FPR) to activate NF-κB. (b) Leakage of mtDNA to the cytosol activates Toll-Like-Receptor (TLR), cyclic GMP-AMP synthase-simulator of interferon genes (cGAS-STING) pathways, and NLRP3 inflammasome. (c) ATP and cardiolipin activate NLRP3 inflammasome. (d) Mitochondrial ROS (mtROS) activates NLRP3 inflammasome and mitogen-activated protein kinase (MAPK) signaling. (e) Binding of mtDNA to cytosolic TFAM activates the TLR pathway. (f) Cytosolic cytochrome C (Cyt C) reduces IL-12 and increases lymphocyte cell death. (Lower) Regulation of inflammation pathway by mitochondrial factors. (g) MAVS recruits RIG-I or MDA5 to viral RNA to activate NF-κB and IRF3. (h) ESCIT generates mtROS by binding to TRAF6. (i) MARCH5 ubiquitinates TANK to enhance TRAF6 signaling.

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References

    1. Smith RA, Hartley RC, Cocheme HM, Murphy MP. Mitochondrial pharmacology. Trends Pharmacol Sci. 2012;33:341–352. doi: 10.1016/j.tips.2012.03.010. - DOI - PubMed
    1. Yoo SM, Jung YK. A Molecular Approach to Mitophagy and Mitochondrial Dynamics. Mol Cells. 2018;41:18–26. - PMC - PubMed
    1. Suomalainen A, Battersby BJ. Mitochondrial diseases: the contribution of organelle stress responses to pathology. Nat Rev Mol Cell Biol. 2018;19:77–92. doi: 10.1038/nrm.2017.66. - DOI - PubMed
    1. Leyns CEG, Ulrich JD, Finn MB, et al. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy. Proc Natl Acad Sci U S A. 2017;114:11524–11529. doi: 10.1073/pnas.1710311114. - DOI - PMC - PubMed
    1. Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261:921–923. doi: 10.1126/science.8346443. - DOI - PubMed

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