Exosomes can directly activate target cells through plasma membrane receptors or act as transporters to transport proteins, lipids, non-coding RNA and even viruses to target cells, serving as signaling factors to alter the biological activity and function of target cells (Simon et al. Exosomes are small vesicles secreted by all types of brain cells and play a role in communication between cells through charge transfer or encapsulation. Brain exosomes have a significant impact on the development, activation and regeneration of neurons. In addition, exosomes are reported to be involved in the onset and spread of various neurodegenerative diseases.
In this review, we discuss the content of exosomes derived from major brain cell types and their function under physiological and pathological conditions. Exosomes are nanometer-sized membrane particles that are secreted by cells that transmit information from one cell to another. The information contained in exosomes prominently includes their protein and RNA payloads. Exosomal microRNAs, in particular, can potently alter and the transcriptome of recipient cells is fundamental.
Here we summarize what is known about the biogenesis, content, and transmission of exosomes, with a focus on cardiovascular physiology and pathophysiology. We also highlight some of the issues currently being investigated in relation to these extracellular membrane vesicles and their potential in diagnostic and therapeutic applications. Tumor exosomes and resistance to therapy. Exosomes are becoming a potential factor contributing to cancer progression, adding another dimension to the complexity of the tumor microenvironment.
Therefore, it is conceivable that cancer exosomes could serve as a therapeutic target. Efforts to suppress the horizontal transfer of miRs from cancer cells to intravenous cells through exosomes attenuate angiogenesis and metastasis (9). Exosomes derived from tumor stroma have also been linked to cancer chemoresistance (34, 8), supporting the idea that targeting specific functions of exosomes could improve the response to therapies. Exosomes can carry a defined set of miRs that transfer a resistance phenotype to sensitive cancer cells by altering cell cycle control and inducing anti-apoptosis programs.
The depletion of these exosomes limits the invasive characteristics of cancer cells (3). The transfer of fibroblast-derived exosomes to breast cancer cells can confer resistance to chemotherapy and radiation therapy by activating STAT1-dependent antiviral signaling and NOTCH3 signaling in cancer cells (8). Exosomes can also negatively affect chemotherapy treatment by removing chemotherapeutic agents from target cancer cells (92, 9). Cisplatin and doxorubicin are found in cancer cells derived from cancer cells.
exosomes in a post-treatment environment (92, 9). HER-2+ breast exosomes that overexpress HER-2) cancer cells inhibit the antiproliferative activity induced by trastuzumab (2); therefore, removing HER-2+ exosomes from the blood of patients with breast cancers that overexpress HER-2 could improve patients' responses to trasuzumab (9). The depletion of exosomes from the blood of cancer patients can also minimize immune tolerance potentially mediated by exosomes (9). While exosome depletion may offer treatment benefits for cancer patients, understand the full effect of exosome depletion on the body (9).
Exosomes transfer not only proteins and lipids, but also mRNA and microRNA into acceptor cells, and it has been demonstrated in in vitro experiments that these RNAs have functional effects on recipient cells. The role of exosomes in immune regulation is probably due to the transfer and presentation of antigenic peptides, the delivery of DNA-inducing cGAS-STING (cyclic stimulator of interferon genes with GMP-AMP synthase) signaling to recipient cells (an immune pathway in which the detection of cytosolic DNA triggers the expression of inflammatory genes and a response to type I IFN), the manipulation of gene expression using exosomal miRNA and the induction of different pathways of signaling by surface ligands present in exosomes. These findings support that exosomes derived from cancer cells can change the metabolism of non-cancerous cells, including adipocytes and pancreatic islet cells, thus functionally contributing to the development of cachexia and paraneoplastic syndrome. In this way, they promoted the exosome-mediated transfer of functionally active intercellular lncRNA as an intercellular signaling mechanism in the CHC. It was also demonstrated that the role of exosomal DNA in the immune response is functionally relevant to cancer progression.
With so little knowledge about their basic physiological functions, it may seem difficult to understand how exosomes have been implicated in the pathogenesis of so many disparate disease states. The release of neuronal exosomes is triggered by the entry of Ca2+ through N-methyl-D-aspartate (NMDA) and î±-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptors at glutamatergic synapses, suggesting that exosome release may be part of normal synaptic physiology18. The exosomal secretion of various cell types exists in almost all types of body fluids and functions as mediators of communication between cells, making exosomes play a crucial role in physiological and pathological processes. The effects of exosomes on recipient cells can be different because of their varied expression of cell surface receptors, and such functional heterogeneity can result in one set of exosomes inducing cell survival, another set inducing apoptosis, and a different set inducing immunomodulation, etc. The rate of biogenesis of exosomes is largely unknown and probably differs between cell types and their physiological or pathological state. This effort is greatly encouraged by the intrinsic properties of exosomes to efficiently cross the blood-brain barrier, a vascular network that functions as a selective filter to prevent drugs or toxins from reaching the brain (28, 142-14).
The different mechanisms and pathways associated with exosome uptake (6, 25, 2) and the presumed specificity of exosomes for certain cell types add complexity to the function of exosomes in intercellular communication. In addition to their fundamental role in normal brain function, exosomes have also been implicated in the spread of neurodegenerative diseases12,21. However, the production of electric vehicles by cells seems to go beyond a simple protein recycling function, as initially reported for the transferrin receptor in reticulocyte maturation (8), and varies depending on the cellular origin, metabolic state and environment of the cells.
