Exosomes as mediators of neuroinflammation

Gupta, Archana; Pulliam, Lynn

doi:10.1186/1742-2094-11-68

Cited by 274 publications

(238 citation statements)

References 78 publications

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“…In principle, one could also implant the engineered parent cells in vivo to reduce the injection frequency. Moreover, exosomes mediated cargo transfer from transplanted Mϕs to contiguous brain resident cells such as endothelial cells and neurons [12, 14, 19, 20], and facilitated spreading of disease-relevant proteins inside the brain and into CSF [21, 22], suggesting exosomes may facilitate drug distribution in the brain upon penetrating the BBB.…”

Section: Discussionmentioning

confidence: 99%

“…The functional activity of Mϕs in these applications can be in part mediated by exosomes that share common elements, such as LFA-1 involved in the diapedesis of Mϕs across endothelial barriers [18]. The Mϕ exosomes can mediate the transfer of their cargo to other brain resident cells [12, 14, 19, 20], or facilitate spreading of viruses and virus proteins from periphery to and within the brain [21, 22]. …”

Section: Introductionmentioning

confidence: 99%

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Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain

et al. 2017

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Recent work has stimulated interest in the use of exosomes as nanocarriers for delivery of small drugs, RNAs, and proteins to the central nervous system (CNS). To overcome the blood-brain barrier (BBB), exosomes were modified with brain homing peptides that target brain endothelium but likely to increase immune response. Here for the first time we demonstrate that there is no need for such modification to penetrate the BBB in mammals. The naïve macrophage (Mϕ) exosomes can utilize, 1) on the one hand, the integrin lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), and, 2) on the other hand, the carbohydrate-binding C-type lectin receptors, to interact with brain microvessel endothelial cells comprising the BBB. Notably, upregulation of ICAM-1, a common process in inflammation, promotes Mϕ exosomes uptake in the BBB cells. We further demonstrate in vivo that naïve Mϕ exosomes, after intravenous (IV) administration, cross the BBB and deliver a cargo protein, the brain derived neurotrophic factor (BDNF), to the brain. This delivery is enhanced in the presence of brain inflammation, a condition often present in CNS diseases. Taken together, the findings are of interest to basic science and possible use of Mϕ-derived exosomes as nanocarriers for brain delivery of therapeutic proteins to treat CNS diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain

et al. 2017

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“…8b). Microvesicles are involved in intercellular communication [221, 222], coagulation [223], inflammation [223, 224], tumorigenesis [191], migration [225] and parasitism [226]. Microvesicles are also proposed to play a role during RBC senescence by two opposite mechanisms.…”

Section: Physiopathological Significancementioning

confidence: 99%

Recent progress on lipid lateral heterogeneity in plasma membranes: From rafts to submicrometric domains

Carquin

D’Auria

Pollet

et al. 2016

Progress in Lipid Research

128

115

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The concept of transient nanometric domains known as lipid rafts has brought interest to reassess the validity of the Singer-Nicholson model of a fluid bilayer for cell membranes. However, this new view is still insufficient to explain the cellular control of surface lipid diversity or membrane deformability. During the past decade, the hypothesis that some lipids form large (submicrometric/mesoscale vs nanometric rafts) and stable (> min vs sec) membrane domains has emerged, largely based on indirect methods. Morphological evidence for stable submicrometric lipid domains, well-accepted for artificial and highly specialized biological membranes, was further reported for a variety of living cells from prokaryotes to yeast and mammalian cells. However, results remained questioned based on limitations of available fluorescent tools, use of poor lipid fixatives, and imaging artifacts due to non-resolved membrane projections. In this review, we will discuss recent evidence generated using powerful and innovative approaches such as lipid-specific toxin fragments that support the existence of submicrometric domains. We will integrate documented mechanisms involved in the formation and maintenance of these domains, and provide a perspective on their relevance on membrane deformability and regulation of membrane protein distribution.

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“…Gupta and Pulliam, 2014). Exosomes are capable of inducing pro-inflammatory effects, including antigen presentation, cellular migration, apoptosis induction, and inflammatory cytokine release (Wahlund et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Exosomal biomarkers in Down syndrome and Alzheimer's disease

Hamlett

Ledreux

Potter³

et al. 2018

Free Radical Biology and Medicine

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Every person with Down syndrome (DS) has the characteristic features of Alzheimer’s disease (AD) neuropathology in their brain by the age of forty, and most go on to develop AD dementia. Since people with DS show highly variable levels of baseline function, it is often difficult to identify early signs of dementia in this population. The discovery of blood biomarkers predictive of dementia onset and/or progression in DS is critical for developing effective clinical diagnostics. Our recent studies show that neuron-derived exosomes, which are small extracellular vesicles secreted by most cells in the body, contain elevated levels of amyloid-beta peptides and phosphorylated-Tau that could indicate a preclinical AD phase in people with DS starting in childhood. We also found that the relative levels of these biomarkers were altered following dementia onset. Exosome release and signaling are dependent on cellular redox homeostasis as well as on inflammatory processes, and exosomes may be involved in the immune response, suggesting a dual role as both triggers of inflammation in the brain and propagators of inflammatory signals between brain regions. Based on recently reported connections between inflammatory processes and exosome release, the elevated neuroinflammatory state observed in people with DS may affect exosomal AD biomarkers. Herein, we discuss findings from studies of people with DS, people with DS and AD (DS-AD), and mouse models of DS showing new connections between neuroinflammatory pathways, oxidative stress, exosomes, and exosome-mediated signaling, which may inform future AD diagnostics, preventions, and treatments in the DS population as well as in the general population.

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Exosomes as mediators of neuroinflammation

Cited by 274 publications

References 78 publications

Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain

Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain

Recent progress on lipid lateral heterogeneity in plasma membranes: From rafts to submicrometric domains

Exosomal biomarkers in Down syndrome and Alzheimer's disease

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