Astrocyte-derived extracellular vesicles enhance the survival and electrophysiological function of human cortical neurons in vitro

Chun, Changho; Smith, André; Kim, Hye-Jin; Kamenz, Dana S.; Lee, Jung Hyun; Lee, Jong Bum; Mack, David L.; Bothwell, Mark; Clelland, Claire D.; Kim, Deok Ho

doi:10.1016/j.biomaterials.2021.120700

Cited by 21 publications

(19 citation statements)

References 57 publications

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“…Among the cargos found inside the EVs of this study, heat shock proteins, LRP1, alpha-synuclein, and apoE were detected, among others. [ 462 ]. However, the previous study did not evaluate the effect of the different apoE isoforms, which would be of great interest in the future.…”

Section: Apoe In Alzheimer’s Diseasementioning

confidence: 99%

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Fernández-Calle

Konings

Frontiñán-Rubio

et al. 2022

Mol Neurodegeneration

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ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-β plaques and neurofibrillary tangles of hyperphosphorylated aggregated tau protein. This review aims to broadly and extensively describe the differential aspects concerning apoE. Starting from the evolution of apoE to how APOE's single-nucleotide polymorphisms affect its structure, function, and involvement during health and disease. This review reflects on how APOE's polymorphisms impact critical aspects of AD pathology, such as the neuroinflammatory response, particularly the effect of APOE on astrocytic and microglial function and microglial dynamics, synaptic function, amyloid-β load, tau pathology, autophagy, and cell–cell communication. We discuss influential factors affecting AD pathology combined with the APOE genotype, such as sex, age, diet, physical exercise, current therapies and clinical trials in the AD field. The impact of the APOE genotype in other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies and Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, is also addressed. Therefore, this review gathers the most relevant findings related to the APOE genotype up to date and its implications on AD and CNS pathologies to provide a deeper understanding of the knowledge in the APOE field.

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Section: Apoe In Alzheimer’s Diseasementioning

confidence: 99%

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Fernández-Calle

Konings

Frontiñán-Rubio

et al. 2022

Mol Neurodegeneration

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“… Bu et al (2020) performed a series of in vitro experiments and demonstrated that astrocyte-derived exosomes promoted hypoxia-inhibited PC12 cell activity and suppressed cell apoptosis. Likewise, Chun et al (2021) reported that astrocyte-derived EVs enhanced the survival and electrophysiological function of human cortical neurons. Notably, neuronal apoptosis was significantly increased upon treatment with conditioned medium from necroptotic astrocytes via EVs delivery ( Chen et al, 2021 ).…”

Section: Extracellular Vesicles-derived From Neurons/neurogliocytes R...mentioning

confidence: 93%

“…Concerning the EVs derived from microglia, EV derived from both hypoxic and normoxic microglia can repress neuronal apoptosis and promote neuronal viability in hypoxic cortical neurons ( Li et al, 2021a ; Zhang et al, 2021a ). To date, many studies have assessed the effect of EVs derived from neurons/glial cells in the regulation of apoptosis in CNS diseases ( Song et al, 2019a ; Xu et al, 2019 ; Bu et al, 2020 ; Casella et al, 2020 ; Datta Chaudhuri et al, 2020 ; Gao et al, 2020 ; Nogueras-Ortiz et al, 2020 ; Zhang et al, 2021a ; Chen et al, 2021 ; Chun et al, 2021 ; Qi et al, 2021 ). The characteristics of these studies are summarized in Table 1 .…”

Section: Extracellular Vesicles-derived From Neurons/neurogliocytes R...mentioning

confidence: 99%

The Emerging Role of Extracellular Vesicle Derived From Neurons/Neurogliocytes in Central Nervous System Diseases: Novel Insights Into Ischemic Stroke

Kang

Xin

et al. 2022

Front. Pharmacol.

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Neurons and neurogliocytes (oligodendrocytes, astrocytes, and microglia) are essential for maintaining homeostasis of the microenvironment in the central nervous system (CNS). These cells have been shown to support cell-cell communication via multiple mechanisms, most recently by the release of extracellular vesicles (EVs). Since EVs carry a variety of cargoes of nucleic acids, lipids, and proteins and mediate intercellular communication, they have been the hotspot of diagnosis and treatment. The mechanisms underlying CNS disorders include angiogenesis, autophagy, apoptosis, cell death, and inflammation, and cell-EVs have been revealed to be involved in these pathological processes. Ischemic stroke is one of the most common causes of death and disability worldwide. It results in serious neurological and physical dysfunction and even leads to heavy economic and social burdens. Although a large number of researchers have reported that EVs derived from these cells play a vital role in regulating multiple pathological mechanisms in ischemic stroke, the specific interactional relationships and mechanisms between specific cell-EVs and stroke treatment have not been clearly described. This review aims to summarize the therapeutic effects and mechanisms of action of specific cell-EVs on ischemia. Additionally, this study emphasizes that these EVs are involved in stroke treatment by inhibiting and activating various signaling pathways such as ncRNAs, TGF-β1, and NF-κB.

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“…In human astrocyte-derived exosomes, other proteins with neuroprotective effects have been identified by proteomic analysis, such as heat shock protein 90 alpha family class B member 1 (HSP90AB1), lipoprotein receptor-related protein 1 (LRP1), and apolipoprotein E (APOE), which negatively regulates neuronal apoptosis. In addition, these exosomes contain proteins that regulate neuronal excitability such as potassium channel tetramerization domain containing 12 (KCTD12), glucose-6-phosphate dehydrogenase (G6PD), kinesin family member 5B (KIF5B), and spectrin-alpha non-erythrocytic 1 (SPTAN1) ( Chun et al, 2021 ).…”

Section: Astrocyte-derived Exosomesmentioning

confidence: 99%

Neuroprotective and Neurotoxic Effects of Glial-Derived Exosomes

Oyarce

Cepeda

Lagos

et al. 2022

Front. Cell. Neurosci.

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Exosomes derived from glial cells such as astrocytes, microglia, and oligodendrocytes can modulate cell communication in the brain and exert protective or neurotoxic effects on neurons, depending on the environmental context upon their release. Their isolation, characterization, and analysis under different conditions in vitro, in animal models and samples derived from patients has allowed to define the participation of other molecular mechanisms behind neuroinflammation and neurodegeneration spreading, and to propose their use as a potential diagnostic tool. Moreover, the discovery of specific molecular cargos, such as cytokines, membrane-bound and soluble proteins (neurotrophic factors, growth factors, misfolded proteins), miRNA and long-non-coding RNA, that are enriched in glial-derived exosomes with neuroprotective or damaging effects, or their inhibitors can now be tested as therapeutic tools. In this review we summarize the state of the art on how exosomes secretion by glia can affect neurons and other glia from the central nervous system in the context of neurodegeneration and neuroinflammation, but also, on how specific stress stimuli and pathological conditions can change the levels of exosome secretion and their properties.

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Astrocyte-derived extracellular vesicles enhance the survival and electrophysiological function of human cortical neurons in vitro

Cited by 21 publications

References 57 publications

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

The Emerging Role of Extracellular Vesicle Derived From Neurons/Neurogliocytes in Central Nervous System Diseases: Novel Insights Into Ischemic Stroke

Neuroprotective and Neurotoxic Effects of Glial-Derived Exosomes

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