Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders
Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress and mitochondrial dysfunction are considered key ri...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/15/2364 |
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| author | Cláudia M. Deus Henrique Tavares Margarida Beatriz Sandra Mota Carla Lopes |
| author_facet | Cláudia M. Deus Henrique Tavares Margarida Beatriz Sandra Mota Carla Lopes |
| author_sort | Cláudia M. Deus |
| collection | DOAJ |
| description | Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described. Recently, a new mechanism of intercellular signalling mediated by small extracellular vesicles (EVs) has been identified. EVs are nanosized particles (30–150 nm) with a bilipid membrane that carries cell-specific bioactive cargos that participate in physiological or pathological processes. Damage-associated molecular patterns (DAMPs) are cellular components recognised by the immune receptors of microglia, inducing or aggravating neuroinflammation in neurodegenerative disorders. Diverse evidence links mitochondrial dysfunction and inflammation mediated by mitochondrial-DAMPs (mtDAMPs) such as mitochondrial DNA, mitochondrial transcription factor A (TFAM) and cardiolipin, among others. Mitochondrial-derived vesicles (MDVs) are a subtype of EVs produced after mild damage to mitochondria and, upon fusion with multivesicular bodies are released as EVs to the extracellular space. MDVs are particularly enriched in mtDAMPs which can induce an immune response and the release of pro-inflammatory cytokines. Importantly, growing evidence supports the association between mitochondrial dysfunction, EV release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders. |
| first_indexed | 2024-03-09T05:31:14Z |
| format | Article |
| id | doaj.art-57f94240fd5742b08ba458c4759df302 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T05:31:14Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-57f94240fd5742b08ba458c4759df3022023-12-03T12:32:23ZengMDPI AGCells2073-44092022-08-011115236410.3390/cells11152364Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative DisordersCláudia M. Deus0Henrique Tavares1Margarida Beatriz2Sandra Mota3Carla Lopes4CNC—Center for Neuroscience and Cell Biology, CIBB—Center for Innovative Biomedicine and Biotechnology, III-Institute of Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, CIBB—Center for Innovative Biomedicine and Biotechnology, III-Institute of Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, CIBB—Center for Innovative Biomedicine and Biotechnology, III-Institute of Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, CIBB—Center for Innovative Biomedicine and Biotechnology, III-Institute of Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, CIBB—Center for Innovative Biomedicine and Biotechnology, III-Institute of Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, PortugalNeuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described. Recently, a new mechanism of intercellular signalling mediated by small extracellular vesicles (EVs) has been identified. EVs are nanosized particles (30–150 nm) with a bilipid membrane that carries cell-specific bioactive cargos that participate in physiological or pathological processes. Damage-associated molecular patterns (DAMPs) are cellular components recognised by the immune receptors of microglia, inducing or aggravating neuroinflammation in neurodegenerative disorders. Diverse evidence links mitochondrial dysfunction and inflammation mediated by mitochondrial-DAMPs (mtDAMPs) such as mitochondrial DNA, mitochondrial transcription factor A (TFAM) and cardiolipin, among others. Mitochondrial-derived vesicles (MDVs) are a subtype of EVs produced after mild damage to mitochondria and, upon fusion with multivesicular bodies are released as EVs to the extracellular space. MDVs are particularly enriched in mtDAMPs which can induce an immune response and the release of pro-inflammatory cytokines. Importantly, growing evidence supports the association between mitochondrial dysfunction, EV release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders.https://www.mdpi.com/2073-4409/11/15/2364extracellular vesiclesneurodegenerative disordersmitochondrial damage-associated molecular patternsinflammation |
| spellingShingle | Cláudia M. Deus Henrique Tavares Margarida Beatriz Sandra Mota Carla Lopes Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders Cells extracellular vesicles neurodegenerative disorders mitochondrial damage-associated molecular patterns inflammation |
| title | Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders |
| title_full | Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders |
| title_fullStr | Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders |
| title_full_unstemmed | Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders |
| title_short | Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders |
| title_sort | mitochondrial damage associated molecular patterns content in extracellular vesicles promotes early inflammation in neurodegenerative disorders |
| topic | extracellular vesicles neurodegenerative disorders mitochondrial damage-associated molecular patterns inflammation |
| url | https://www.mdpi.com/2073-4409/11/15/2364 |
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