Microvesicles: Novel Biomarkers for Neurological Disorders

Abstract

Microvesicles (MVs) are released by most cell types in physiological conditions, but their number is often increased upon cellular activation or neoplastic transformation. This suggests that their detection may be helpful in pathological conditions to have information on activated cell types and, possibly, on the nature of the activation. This could be of paramount importance in districts and tissues that are not accessible to direct examination, such as the central nervous system. Increased release of MVs has been described to be associated to the acute or active phase of several neurological disorders. While the subcellular origin of MVs (exosome or ectosomes) is basically never addressed in these studies because of technical limitations, the cell of origin is always identified. Endothelium- or platelet-derived MVs, detected in plasma or serum, are linked to neurological pathologies with a vascular or ischemic pathogenic component, and may represent a very useful marker to support therapeutic choices in stroke. In neuroinflammatory disorders, such as multiple sclerosis, MVs of oligodendroglial, or microglial origin have been described in the cerebrospinal fluid and may carry, in perspective, additional information on the biological alterations in their cell of origin. Little specific evidence is available in neurodegenerative disorders and, specifically, MVs of neural origin have never been investigated in these pathologies. Few data have been reported for neuroinfection and brain trauma. In brain tumors, despite the limited number of studies performed, results are very promising and potentially close to clinical translation. We here review all currently available data on the detection of MVs in neurological diseases, limiting our search to exclusively human studies. Current literature and our own data indicate that MVs detection may represent a very promising strategy to gain pathogenic information, identify therapeutic targets, and select specific biomarkers for neurological disorders.

Microglia convert aggregated amyloid-β into neurotoxic forms through the shedding of microvesicles

“…Notably, microglia-derived MVs in the cerebrospinal fluid (CSF) have been recently identified as a novel biomarker of brain inflammation in humans. 30,31 The observation that typical proteins of EMVs, like flotilin, accumulate in the plaques of AD brain, 32 together with evidence that activated microglia constantly surround amyloid deposits, 33 prompted us to investigate whether EMVs may be involved in the spatiotemporal propagation of Ab pathology through the brain. Here we show that production of MVs is extremely high in patients with AD and that microglial MVs, either shed in vitro or isolated from the CSF of AD patients, promote generation of soluble neurotoxic Ab species, thereby acting as potent drivers of neuronal damage.…”

Possible role of microparticles in neuroimmune signaling of microglial cells

“…MPs may exhibit immunomodulatory and biological properties similar to DAMPs, such as HMGB1 and TFAM. [13][14][15][16] Several studies have investigated the role of MPs as mediators of astrocyte-neuron communication; [15,16,27] however, to date the role of MPs as mediators in microglia communication with neurons, astrocytes, and other microglia remains less characterized.…”

“…[15,16,27] Since MP release is upregulated upon activation and during apoptosis or necrosis; we hypothesized that MPs may act as endogenous DAMPs with immunomodulatory properties similar to HMGB1 or TFAM. [15,29,30] We demonstrated that human mononuclear phagocytes release MPs when activated by pro-inflammatory molecules.…”

“…MP release from microglia is upregulated following their activation and such microliaderived MPs appear to possess immunomodulatory properties similar to HMGB1. [13][14][15][16] Originally considered as inert platelet by-products, MPs are now known to be a heterogeneous population of membrane-derived vesicles ranging in diameter from 0.1 to 1 μm, which participate in intercellular signaling. [17,18] The structural composition and content of MPs differs based on a variety of factors, including the cell type of origin and the nature of the inducing stimulus.…”

Therapeutic and diagnostic applications of extracellular vesicles

“…HIV, Epstein-bar, hepatitis C) to mediate their spread, making EVs valuable tools to detect viral diseases as well [228]. Furthermore, EVs are associated with neurological, metabolic, cardiovascular and kidney conditions and are therefore also proposed as biomarkers for these diseases [229][230][231].…”