Diagnostic and therapeutic potentials of exosomes in CNS diseases

Abstract

A newly discovered cell-to-cell communication system involves small, membrane-enveloped nanovesicles, called exosomes. We describe here how these extracellular nanoparticles were discovered and how it became gradually apparent that they play fundamental roles in regulation of physiological functions and pathological processes. Exosomes enable intercellular communication by transporting genetic material, proteins and lipids to cells in their vicinity or at distant sites, and subsequently regulating functions of targeted cells. Relatively recent experiments indicate that exosomes are released also by CNS cells, including cortical and hippocampal neurons, glial cells, astrocytes and oligodendrocytes, and that exosomes have significant impact on pathophysiology of the brain. How it is decided what individual exosomes will carry to their targets is not understood, but it appears that the contents may represent “signature cargos” that are characteristic for various conditions. Exploration of such characteristics could result in discovery of novel diagnostic biomarkers. Exosomes are also promising as a vehicle for therapeutic delivery of micro RNA or other compounds. How to deliver exosomes to selected sites has been a tantalizing question. Recent experiments revealed that at least some exosomes carry antibodies on their surface, suggesting that it may be feasible to deliver exosomes to unique sites based on the recognition of antigens by those antibodies. This discovery implies that rather precise targeting of both natural and engineered exosomes may be feasible. This would reduce distribution volume of therapeutics, and consequently minimize their side effects.

Glia–neuron interactions in the mammalian retina

“…AQP4 influences many process (the volume of the extracellular space, waste clearance, potassium buffering, cell migration and calcium signalling: Nagelhus and Ottersen, 2013) and significantly, its expression is altered in diabetic retinopathy (Qin et al, 2012). Astrocytes may play a role in the transport of exosomes with different cargos between neurons (Edelstein and Smythies, 2014;Kawikova and Askenase, 2014). In a laser-induced choroidal neovascularisation (CNV) model, retinal astrocytes release exosomes containing anti-angiogenic compounds that protect the eye from the deleterious effects of neovascularisation (Hajrasouliha et al, 2013).…”

Exosome mediated communication within the tumor microenvironment

“…Cancer derived exosomes have a vast array of content composed of microRNAs, mRNAs, transcription factors, proteins, and lipids (Figure 2 [2,[44][45][46][47][48][49]). The content is highly variable and dependent on cell origin, but regardless of origin, the contents of exosomes are highly functional and exert powerful effects in recipient cells.…”

Exosomes in stroke pathogenesis and therapy

“…Neurons and glia actively communicate with each other to coordinate axonal growth and myelination, and emerging data suggest that exosomes released by neurons and glia contribute to these processes (61,83,84). Exosomes released by cultured cortical neurons carried the neuronal-specific protein L1 cell adhesion molecule (L1CAM) and the GluR2/3 subunits, but not the NR1 subunits, of glutamate receptors (85,86).…”