Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders

Version 1 : Received: 4 July 2022 / Approved: 5 July 2022 / Online: 5 July 2022 (14:34:37 CEST)
Version 2 : Received: 5 July 2022 / Approved: 6 July 2022 / Online: 6 July 2022 (09:16:21 CEST)

A peer-reviewed article of this Preprint also exists.

Deus, C.M.; Tavares, H.; Beatriz, M.; Mota, S.; Lopes, C. Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders. Cells 2022, 11, 2364. Deus, C.M.; Tavares, H.; Beatriz, M.; Mota, S.; Lopes, C. Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders. Cells 2022, 11, 2364.

Journal reference: Cells 2022, 11, 2364
DOI: 10.3390/cells11152364

Abstract

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 recognized 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, 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 (MVBs), 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, EVs release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders.

Keywords

Extracellular vesicles; neurodegenerative disorders; mitochondrial damage-associated molecular patterns; inflammation

Subject

LIFE SCIENCES, Immunology

Comments (1)

Comment 1
Received: 6 July 2022
Commenter: Carla Lopes
Commenter's Conflict of Interests: Author
Comment: Cláudia M. Deus 1#, Henrique Tavares 1#, Margarida Beatriz 1, Sandra Mota 1* & Carla Lopes 1,*
1    CNC – Center for Neuroscience and Cell Biology, CIBB - Center for Innovative Biomedicine and Biotechnology, III- Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal; cmcdeus@cnc.uc.pt; henriquer99@hotmail.com; margaridabeatriz@live.com.pt;
*      Corresponding author: Carla Lopes, PhD. Sandra Mota, PhDCNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building (Lot 8A), Biocant Park, 3060-197 Cantanhede, Portugal; Telephone: +351-231-249-235; Fax: +351-231-249-170; carla.lopes@cnc.uc.pt; sandra.mota@cnc.uc.pt
#             Both authors contributed equally.   
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