Extracellular vesicles (EVs) are released from many cell types including normal and pathological cells and range 30-1000 nm in size. and induced apoptosis . In another study mammary tumor derived EVs inhibited natural killer (NK) cell cytotoxic activity . EVs from glioblastoma and melanoma cells have been shown to induce angiogenesis through modulation of endothelial cells [50-52]. In addition melanoma-derived EVs condition sentinel lymph nodes for metastasis as well as educate bone marrow progenitors toward a pro-vasculogenic phenotype via receptor tyrosine kinases [12 53 Enhancement of the tumor microenvironment by EVs has also been observed from both the primary malignancy site as well as from bone marrow for breast ovarian and lung cancers [54-56]. Whereas cancer-derived EVs are able to alter the bone marrow progenitor cell phenotype as well as the phenotypes of other types of cells in healthy tissue it remains to be decided if EVs BIIB021 from diseased neuronal cells affect normal neural stem/progenitor cells in the adult brain (Box 2). A compromised stem/progenitor cell may not be able to repair or replace lost neural circuitry components BIIB021 which would lead to a stem cell pathology . One of the major defining attributes of an adult stem/progenitor cell in addition to its residence in adult poietic niches for maintenance of tissues homeostasis during normal adult neurogenesis (Box 1) is usually its ability to repair and replace at-risk and lost cells following tissue injury or disease. Examples have been reported of human neural stem/progenitor cells with altered growth processes which are indicative of regeneration failure in neurodegenerative diseases such as PD . Further adult stem cells can generate too much tissue and contribute to an abnormal growth milieu in CNS neoplasias including glioblastoma . It remains to be explored how EVs contribute to the pathology of neural stem/progenitor cells observed in these diseases (Box 2). Box 1 Neurogenesis in the adult human brain Neurogenesis occurs in the human brain throughout adulthood. The well-studied regions known to harbor neural stem and progenitor cells are the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. However other regions within the brain have been shown to regenerate new mature cells. Neural stem and progenitor cells have been shown to give rise to neurons astrocytes BIIB021 and oligodendrocytes. Adult neurogenesis can be triggered by injury or disease in an effort to replace repair or salvage affected brain tissue. However with disease neurogenic attempts often fail to fully recover normal brain function damaged by pathogenesis. In Huntington’s disease (HD) there is increased proliferation of stem/progenitor cells in the SVZ yet the increase is insufficient to compensate for the cells that have degenerated. In Parkinson’s disease (PD) satellite cells within the substantia nigra maintain the potential for neurogenesis yet there appear to be too few without the right signals to stimulate proliferation or differentiation. In the case of glioma an over-abundance of stem/progenitor cells may potentiate the cancer itself rather than protect the normal tissue of the brain. Induction of neurogenesis in Alzheimer’s disease (AD) patients appears to have a beneficial impact on disease progression. While mechanisms for brain repair appear to be intrinsic they fail to fully recover the diseased brain from degeneration . EVs may thus provide a common mechanism for disease propagation between neurodegenerative diseases and cancers. There are many contributors to disease initiation and propagation including genetic susceptibility environmental exposure aging mutagens and/or epigenetic factors. We propose that EVs could also play a role in the KSHV K8 alpha antibody initiation and/or spread of disease making these seemingly distinct diseases comparable in nature to one another. In this BIIB021 way we suggest that cancers and neurodegenerative diseases could be comparable in onset and propagation via our growing understanding of EVs and their role in initiating or enhancing disease spread. We believe that parallels can be drawn in concern to the treatment of neurodegenerative diseases and cancer as well as the identification of biomarkers for each disease. Therapeutic implications for EVs Discovery of disease-specific biomarkers housed on and within EVs is essential to better facilitate real-time monitoring of patient disease risk course and.
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