Role of Exosomes in Brain Diseases

Zhang, Nan; Li, Ting; Chen, Jinzhi; Jiang, Liping; Ouyang, Xin; Zuo, Lielian

doi:10.3389/fncel.2021.743353

Cited by 30 publications

(21 citation statements)

References 160 publications

(181 reference statements)

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“…Given their ubiquity in extracellular fluids (8) and extracellular matrices (23,25), organisms have evolved to use exosomes in many physiological processes, including fertilization (18,26,40), development (40)(41)(42)(43), blood homeostasis (19,20,44), bone formation (22,23,45), immunity (31,(46)(47)(48), neuronal function(49), and many others (1,50). Exosomes are also co-opted in many diseases, most obviously in viral infections (2,(51)(52)(53)(54)(55) but also in cancers (30,(56)(57)(58), neuronal disorders (59,60), and inflammatory diseases (61)(62)(63).…”

Section: Introductionmentioning

confidence: 99%

A shared, stochastic pathway mediates exosome protein budding along plasma and endosome membranes

Fordjour

Guo

et al. 2022

Journal of Biological Chemistry

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Section: Introductionmentioning

confidence: 99%

A shared, stochastic pathway mediates exosome protein budding along plasma and endosome membranes

Fordjour

Guo

et al. 2022

Journal of Biological Chemistry

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“…Notably, exosomes are small extracellular vesicles with a diameter of 30–100 nm and include carrying proteins, nucleic acids, and lipids that mediate cell-to-cell signaling to regulate various functions of the host cell. Exosomes can serve as ideal carriers for the delivery of protein- or RNA-based therapeutic drugs to the brain and are potentially valuable biomarkers for the clinical diagnosis and treatment of diseases ( Zhang et al, 2021 ). EBV can use exosomes containing viral proteins and various RNAs to cross the BBB, enter target cells through the exosome surface membrane proteins, bind to target cell surface proteins, transfer its cargo to the target cells, affect the signaling pathways of the target cells, trigger various responses in the target cells, and participate in the development of the CNS.…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus and Neurological Diseases

Zhang

Zuo

Jiang

et al. 2022

Front. Mol. Biosci.

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Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a double-stranded DNA virus that is ubiquitous in 90–95% of the population as a gamma herpesvirus. It exists in two main states, latent infection and lytic replication, each encoding viral proteins with different functions. Human B-lymphocytes and epithelial cells are EBV-susceptible host cells. EBV latently infects B cells and nasopharyngeal epithelial cells throughout life in most immunologically active individuals. EBV-infected cells, free viruses, their gene products, and abnormally elevated EBV titers are observed in the cerebrospinal fluid. Studies have shown that EBV can infect neurons directly or indirectly via infected B-lymphocytes, induce neuroinflammation and demyelination, promote the proliferation, degeneration, and necrosis of glial cells, promote proliferative disorders of B- and T-lymphocytes, and contribute to the occurrence and development of nervous system diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, acute cerebellar ataxia, meningitis, acute disseminated encephalomyelitis, and brain tumors. However, the specific underlying molecular mechanisms are unclear. In this paper, we review the mechanisms underlying the role of EBV in the development of central nervous system diseases, which could bebeneficial in providing new research ideas and potential clinical therapeutic targets for neurological diseases.

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“…Recently, exosomes have emerged as a novel and promising candidate approach for AD therapy owing to their unique advantages ( Zhang N. et al, 2021 ; Zhang T. et al, 2021 ). Specifically, exosomes are stable in physiological fluids and can cross the blood-brain barrier, secrete various proteins and RNAs, and mediate the mutual communication between cells.…”

Section: Discussionmentioning

confidence: 99%

Exosomes Derived From M2 Microglia Cells Attenuates Neuronal Impairment and Mitochondrial Dysfunction in Alzheimer’s Disease Through the PINK1/Parkin Pathway

Shen

Yang

et al. 2022

Front. Cell. Neurosci.

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The accumulation of abnormal aggregation of amyloid-β plaques is one of the most distinguishing pathologies of Alzheimer’s disease (AD) and is highly toxic to neurons. Exosomes have demonstrated great potential for AD therapy. However, the impact and underlying mechanism of M2 microglia-derived exosomes (M2-EXOs) in AD progression and outcome are seldom explored. Therefore, we employed an Aβ1-42 oligomer (Aβ)-induced AD model in neuronal HT-22 cells and 7-month-old APP/PS1 mice to investigate the effects of M2-EXOs on AD. We revealed that the AD cell model established by Aβ was accompanied by the upregulation of Aβ1-42, neuronal death, alternation of mitochondrial function and autophagy. M2-EXOs can be internalized by HT-22 cells and MAP2-positive neuronal cells in APP/PS1 mice, and exert neuroprotective functions. Specifically, the administration of M2-EXOs in the AD cell model partially increased cell viability, restored the destruction of mitochondrial membrane potential, and reduced the accumulation of reactive oxygen species inside the mitochondria and cells in a dose-dependent manner. Moreover, we demonstrated that PINK1/Parkin mediated mitophagy was enhanced, while incubation with M2-EXOs decreased beclin1, LC3II, PINK1, and Parkin expression levels. Finally, we observed that compared with APP/PS1 mice treated with PBS, the application of M2-EXOs could decrease Aβ plaque deposition and minus Aβ oligomer expression along with improved PINK1/Parkin pathway-mediated autophagy. Overall, our results imply that M2-EXOs play a protective role in the pathogenesis of AD by ameliorating PINK1/Parkin-mediated mitophagy, indicating that it may provide a novel therapeutic strategy to treat AD.

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Role of Exosomes in Brain Diseases

Cited by 30 publications

References 160 publications

A shared, stochastic pathway mediates exosome protein budding along plasma and endosome membranes

A shared, stochastic pathway mediates exosome protein budding along plasma and endosome membranes

Epstein-Barr Virus and Neurological Diseases

Exosomes Derived From M2 Microglia Cells Attenuates Neuronal Impairment and Mitochondrial Dysfunction in Alzheimer’s Disease Through the PINK1/Parkin Pathway

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