Mitochondrial-derived damage-associated molecular patterns amplify neuroinflammation in neurodegenerative diseases

• Published in: Acta pharmacologica Sinica Vol. 43; no. 10; pp. 2439 - 2447
• Main Authors: Lin, Miao-miao, Liu, Na, Qin, Zheng-hong, Wang, Yan
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.10.2022; Nature Publishing Group
• Subjects: Adenosine triphosphate; Adenosine Triphosphate - metabolism; Alarmins - metabolism; Biomedical and Life Sciences; Biomedicine; Calcium (mitochondrial); Cardiolipin; Cardiolipins - metabolism; Cytochrome c; Cytochromes c - metabolism; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; Glial cells; Humans; Immunology; Inflammation; Inflammation - metabolism; Internal Medicine; Iron - metabolism; Medical Microbiology; Microglia; Mitochondria; Mitochondria - metabolism; Mitochondrial DNA; Molecular modelling; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - metabolism; Neuroinflammatory Diseases - metabolism; Neuronal-glial interactions; Pharmacology/Toxicology; Protein folding; Reactive oxygen species; Reactive Oxygen Species - metabolism; Review; Review Article; Transcription Factors - metabolism; Vaccine; neurodegenerative diseases; mitochondrial dysfunction; neuroinflammation; microglia; mitochondrial-derived damage-associated molecular pattern
• ISSN: 1671-4083; 1745-7254; 1745-7254
• DOI: 10.1038/s41401-022-00879-6

Both mitochondrial dysfunction and neuroinflammation are implicated in neurodegeneration and neurodegenerative diseases. Accumulating evidence shows multiple links between mitochondrial dysfunction and neuroinflammation. Mitochondrial-derived damage-associated molecular patterns (DAMPs) are recognized by immune receptors of microglia and aggravate neuroinflammation. On the other hand, inflammatory factors released by activated glial cells trigger an intracellular cascade, which regulates mitochondrial metabolism and function. The crosstalk between mitochondrial dysfunction and neuroinflammatory activation is a complex and dynamic process. There is strong evidence that mitochondrial dysfunction precedes neuroinflammation during the progression of diseases. Thus, an in-depth understanding of the specific molecular mechanisms associated with mitochondrial dysfunction and the progression of neuroinflammation in neurodegenerative diseases may contribute to the identification of new targets for the treatment of diseases. In this review, we describe in detail the DAMPs that induce or aggravate neuroinflammation in neurodegenerative diseases including mtDNA, mitochondrial unfolded protein response (mtUPR), mitochondrial reactive oxygen species (mtROS), adenosine triphosphate (ATP), transcription factor A mitochondria (TFAM), cardiolipin, cytochrome c , mitochondrial Ca 2+ and iron.