Small but Mighty—Exosomes, Novel Intercellular Messengers in Neurodegeneration

Abstract

Exosomes of endosomal origin are one class of extracellular vesicles that are important in intercellular communication. Exosomes are released by all cells in our body and their cargo consisting of lipids, proteins and nucleic acids has a footprint reflective of their parental origin. The exosomal cargo has the power to modulate the physiology of recipient cells in the vicinity of the releasing cells or cells at a distance. Harnessing the potential of exosomes relies upon the purity of exosome preparation. Hence, many methods for isolation have been developed and we provide a succinct summary of several methods. In spite of the seclusion imposed by the blood–brain barrier, cells in the CNS are not immune from exosomal intrusive influences. Both neurons and glia release exosomes, often in an activity-dependent manner. A brief description of exosomes released by different cells in the brain and their role in maintaining CNS homeostasis is provided. The hallmark of several neurodegenerative diseases is the accumulation of protein aggregates. Recent studies implicate exosomes’ intercellular communicator role in the spread of misfolded proteins aiding the propagation of pathology. In this review, we discuss the potential contributions made by exosomes in progression of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Understanding contributions made by exosomes in pathogenesis of neurodegeneration opens the field for employing exosomes as therapeutic agents for drug delivery to brain since exosomes do cross the blood–brain barrier.

Glioma‑neuronal interactions in tumor progression: Mechanism, therapeutic strategies and perspectives (Review)

“…A previous study observed how the development of rat cortical neurons led to the secretion of exosomes containing GluA2/3 subunits of AMPARs ( 79 ). Similar patterns of exosome secretion were also observed in the differentiated neurons ( 80 ). A previous study indicated that exosomes derived from cortical neurons only bind to neurons and not to glial cells ( 81 ), suggesting that neuron-derived EVs (NEVs) mediate neuron-to-glioma communication indirectly.…”

“…A previous study indicated that exosomes derived from cortical neurons only bind to neurons and not to glial cells ( 81 ), suggesting that neuron-derived EVs (NEVs) mediate neuron-to-glioma communication indirectly. This indicated that the secretion of exosomes is activity-dependent and is specifically mediated by glutamatergic activity involving AMPAR and NMDAR ( 79 , 80 ). The glioma microenvironment renders neurons hyperexcitable due to the high glutamate concentration ( 67 ).…”

Neurospecific Molecules Measured in Periphery in Humans: How Do They Correlate with the Brain Levels? A Systematic Review

“…Exosomes are extracellular vesicles of 50–150 nm in diameter that are released by cells; they play an important role in intercellular communication and, thus, they circulate freely in body fluids, enter target cells, and may easily cross multiple anatomical and physiological boundaries, including the highly selective BBB [ 64 ]. They carry diverse molecular cargoes, such as nucleic acids (DNA, RNA, ncRNA, miRNA), lipids, and proteins that have a footprint reflective of their parental origin (both parent cells and extracellular environment) [ 65 , 66 ]. Compared to other substrates, the discovery of brain exosomes has been delayed.…”

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

“…No matter how the biogenesis of exosomes proceeds, they are composed of phospholipid bilayer structures that encapsulate lipids, proteins, and nucleic acids ( Kumari and Anji, 2022 ). Lipids, an essential part of exosome membrane, include cholesterol, sphingyelin, ceramide, etc.…”