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Picca A, Calvani R, Coelho-Junior HJ, et al. Mitochondrial Dysfunction, Oxidative Stress, and Neuroinflammation: Intertwined Roads to Neurodegeneration. Antioxidants (Basel). 2020;9(8)doi: 10.3390/antiox9080647.
Picca, A., Calvani, R., Coelho-Junior, H. J., Landi, F., Bernabei, R., & Marzetti, E. (2020). Mitochondrial Dysfunction, Oxidative Stress, and Neuroinflammation: Intertwined Roads to Neurodegeneration. Antioxidants (Basel, Switzerland), 9(8), . https://doi.org/10.3390/antiox9080647
Picca, Anna, et al. "Mitochondrial Dysfunction, Oxidative Stress, and Neuroinflammation: Intertwined Roads to Neurodegeneration." Antioxidants (Basel, Switzerland) vol. 9,8 (2020). doi: https://doi.org/10.3390/antiox9080647
Picca A, Calvani R, Coelho-Junior HJ, Landi F, Bernabei R, Marzetti E. Mitochondrial Dysfunction, Oxidative Stress, and Neuroinflammation: Intertwined Roads to Neurodegeneration. Antioxidants (Basel). 2020 Jul 22;9(8). doi: 10.3390/antiox9080647. PMID: 32707949; PMCID: PMC7466131.
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Antioxidants (Basel). 2020 Jul 22;9(8). doi: 10.3390/antiox9080647.

Mitochondrial Dysfunction, Oxidative Stress, and Neuroinflammation: Intertwined Roads to Neurodegeneration.

Antioxidants (Basel, Switzerland)

Anna Picca, Riccardo Calvani, Hélio José Coelho-Junior, Francesco Landi, Roberto Bernabei, Emanuele Marzetti

Affiliations

  1. Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, 00168 Rome, Italy.
  2. Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

PMID: 32707949 PMCID: PMC7466131 DOI: 10.3390/antiox9080647

Abstract

Oxidative stress develops as a response to injury and reflects a breach in the cell's antioxidant capacity. Therefore, the fine-tuning of reactive oxygen species (ROS) generation is crucial for preserving cell's homeostasis. Mitochondria are a major source and an immediate target of ROS. Under different stimuli, including oxidative stress and impaired quality control, mitochondrial constituents (e.g., mitochondrial DNA, mtDNA) are displaced toward intra- or extracellular compartments. However, the mechanisms responsible for mtDNA unloading remain largely unclear. While shuttling freely within the cell, mtDNA can be delivered into the extracellular compartment via either extrusion of entire nucleoids or the generation and release of extracellular vesicles. Once discarded, mtDNA may act as a damage-associated molecular pattern (DAMP) and trigger an innate immune inflammatory response by binding to danger-signal receptors. Neuroinflammation is associated with a large array of neurological disorders for which mitochondrial DAMPs could represent a common thread supporting disease progression. The exploration of non-canonical pathways involved in mitochondrial quality control and neurodegeneration may unveil novel targets for the development of therapeutic agents. Here, we discuss these processes in the setting of two common neurodegenerative diseases (Alzheimer's and Parkinson's disease) and Down syndrome, the most frequent progeroid syndrome.

Keywords: Alzheimer’s disease; DAMPs; Down syndrome; Parkinson’s disease; cytokines; endo-lysosomal system; extracellular vesicles; mitochondrial DNA; mitochondrial quality control; mitophagy

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