Possible role of microparticles in neuroimmune signaling of microglial cells

Schindler, Stephanie M.; Bajwa, Ekta; Little, Jonathan P.; Klegeris, Andis

doi:10.20517/2347-8659.2016.25

Cited by 3 publications

(3 citation statements)

References 58 publications

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“…Moreover, the MPs released by THP-1 cells in response to TFAM were able to activate THP-1 cells in an autocrine manner and led to cytotoxicity as shown by a decrease in SH-SY5Y neuronal cell viability following exposure to supernatant from MP-stimulated monocytic cells. The MPs derived from TFAM-stimulated THP-1 cells also induced the secretion of MCP-1 by THP-1 cells [83]. These results indicate that TFAM may act as a DAMP that can activate microglial cells to release MPs that possess neurotoxic and inflammatory properties and could contribute to neurodegenerative disease pathology.…”

Section: Mitochondrial Transcription Factor a (Tfam)mentioning

confidence: 99%

The Role of Mitochondrial Damage-Associated Molecular Patterns in Chronic Neuroinflammation

Bajwa

Pointer

Klegeris

2019

Mediators of Inflammation

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Mitochondrial dysfunction has been established as a common feature of neurodegenerative disorders that contributes to disease pathology by causing impaired cellular energy production. Mitochondrial molecules released into the extracellular space following neuronal damage or death may also play a role in these diseases by acting as signaling molecules called damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs have been shown to initiate proinflammatory immune responses from nonneuronal glial cells, including microglia and astrocytes; thereby, they have the potential to contribute to the chronic neuroinflammation present in these disorders accelerating the degeneration of neurons. In this review, we highlight the mitochondrial DAMPs cytochrome c (CytC), mitochondrial transcription factor A (TFAM), and cardiolipin and explore their potential role in the central nervous system disorders including Alzheimer’s disease and Parkinson’s disease, which are characterized by neurodegeneration and chronic neuroinflammation.

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Section: Mitochondrial Transcription Factor a (Tfam)mentioning

confidence: 99%

The Role of Mitochondrial Damage-Associated Molecular Patterns in Chronic Neuroinflammation

Bajwa

Pointer

Klegeris

2019

Mediators of Inflammation

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“…Moreover, Schindler et al. [140] also showed in their study that TFAM can stimulate THP‐1 cells to release microparticles (MP), which act as proinflammatory stimulants, leading to MCP‐1 secretion. eATP also activates the P2Y receptors causing an outward potassium movement, leading to a PI‐3K‐dependent chemotaxis of microglia [141].…”

Section: Mitochondrial Damps In Diseasementioning

confidence: 99%

Immunomodulatory role of mitochondrial DAMPs: a missing link in pathology?

2022

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In accordance with the endosymbiotic theory, mitochondrial components bear characteristic prokaryotic signatures, which act as immunomodulatory molecules when released into the extramitochondrial compartment. These endogenous immune triggers, called mitochondrial damage‐associated molecular patterns (mtDAMPs), have been implicated in the pathogenesis of various diseases, yet their role remains largely unexplored. In this review, we summarise the available literature on mtDAMPs in diseases, with a special focus on respiratory diseases. We highlight the need to bolster mtDAMP research using a multipronged approach, to study their effect on specific cell types, receptors and machinery in pathologies. We emphasise the lacunae in the current understanding of mtDAMPs, particularly in their cellular release and the chemical modifications they undergo. Finally, we conclude by proposing additional effects of mtDAMPs in diseases, specifically their role in modulating the immune system.

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“…Activated microglia release MPs carrying IL-1β, and these microgliaderived MPs enhanced inflammatory response by transferring inflammatory stimuli to other microglia (197)(198)(199). A study by Schindler et al (200) using cultured human mononuclear phagocytes demonstrated that microglia-derived MPs induced NF-κB activation, leading to the release of proinflammatory cytokines (200). The role of microglia-derived MPs was further substantiated in a study investigating neuroinflammation following brain traumatic injury whereby the MPs (identified through P2Y12/CD45 + ) derived from neuroinflammation that developed in the brain were released into the circulation and initiated neuroinflammation in naive control animals (201).…”

Section: Mps and Inflammationmentioning

confidence: 99%

Diets and Cellular-Derived Microparticles: Weighing a Plausible Link With Cerebral Small Vessel Disease

Nassir

Ghazali

Hashim

et al. 2021

Front. Cardiovasc. Med.

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Cerebral small vessel disease (CSVD) represents a spectrum of pathological processes of various etiologies affecting the brain microcirculation that can trigger neuroinflammation and the subsequent neurodegenerative cascade. Prevalent with aging, CSVD is a recognized risk factor for stroke, vascular dementia, Alzheimer disease, and Parkinson disease. Despite being the most common neurodegenerative condition with cerebrocardiovascular axis, understanding about it remains poor. Interestingly, modifiable risk factors such as unhealthy diet including high intake of processed food, high-fat foods, and animal by-products are known to influence the non-neural peripheral events, such as in the gastrointestinal tract and cardiovascular stress through cellular inflammation and oxidation. One key outcome from such events, among others, includes the cellular activations that lead to elevated levels of endogenous cellular-derived circulating microparticles (MPs). MPs can be produced from various cellular origins including leukocytes, platelets, endothelial cells, microbiota, and microglia. MPs could act as microthrombogenic procoagulant that served as a plausible culprit for the vulnerable end-artery microcirculation in the brain as the end-organ leading to CSVD manifestations. However, little attention has been paid on the potential role of MPs in the onset and progression of CSVD spectrum. Corroboratively, the formation of MPs is known to be influenced by diet-induced cellular stress. Thus, this review aims to appraise the body of evidence on the dietary-related impacts on circulating MPs from non-neural peripheral origins that could serve as a plausible microthrombosis in CSVD manifestation as a precursor of neurodegeneration. Here, we elaborate on the pathomechanical features of MPs in health and disease states; relevance of dietary patterns on MP release; preclinical studies pertaining to diet-based MPs contribution to disease; MP level as putative surrogates for early disease biomarkers; and lastly, the potential of MPs manipulation with diet-based approach as a novel preventive measure for CSVD in an aging society worldwide.

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Possible role of microparticles in neuroimmune signaling of microglial cells

Cited by 3 publications

References 58 publications

The Role of Mitochondrial Damage-Associated Molecular Patterns in Chronic Neuroinflammation

The Role of Mitochondrial Damage-Associated Molecular Patterns in Chronic Neuroinflammation

Immunomodulatory role of mitochondrial DAMPs: a missing link in pathology?

Diets and Cellular-Derived Microparticles: Weighing a Plausible Link With Cerebral Small Vessel Disease

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