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Manuscript Submission Deadline 31 December 2023

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Research into extracellular vesicles (EVs) biology has increased considerably over the past decade, posing manifold questions regarding their involvement in homeostatic and pathological processes. EVs are nano-sized particles and can be classified broadly into exosomes (40-150 nm), microvesicles (50-2000 nm), or apoptotic bodies (50-5000 nm). New classes of EVs also include smaller exomeres and supermeres (≤ 50 nm) and exophers, which vary widely in size from a ~1.5 μm diameter to the size of an entire cell. In the central nervous system (CNS), EVs are secreted by all cell types, including neurons and glia. EVs carry a cargo of nucleic acids, proteins, and lipids that varies, reflecting their cellular origin and the state of the originating cells. Following their release into the extracellular space, EVs can mediate intercellular communication, synaptic plasticity, antigen presentation, and neurotrophic support in the CNS.

Besides their crucial physiological roles, EVs are thought to propagate pathological age-related processes through miRNA regulation, neuroinflammation, the spread of toxic misfolded proteins, and possibly the spread of viruses. Interestingly, this spread may be mediated by EVs not only within the CNS but also between the CNS and peripheral tissues and organs. Moreover, alterations in EVs may be related to changes in in senescent cells and aging tissues, highlighting a putative role of EVs in the process of aging. At the same time, EVs are thought to contribute to the pathogenesis of various age-related neurodegenerative diseases (NDD), such as Alzheimer’s Disease and other tauopathies, Parkinson’s disease and other synucleinopathies, Huntington’s disease and other poly-glutamine related diseases, among others. However, the exact mechanisms that govern the role of EVs in the neurodegenerative context are not fully understood.

A better understanding of their formation, cargo loading, secretion, and uptake in inter- and intracellular neurogenerative pathways could shed light on the initiation and propagation mechanisms of various NDD, thereby contributing to the identification of effective therapeutic strategies. Notably, several properties of EVs, including the ability to cross the blood-brain barrier or the intimate relationship between their cargo and cell origin, make them excellent candidates for harboring biomarkers or drug delivery systems. Thus, contributing to the knowledge of the abovementioned mechanisms may further increase their potential as reliable diagnostic tools or advanced drug delivery systems to the brain in complex neurodegenerative conditions.

This Research Topic aims to present studies of the most recent developments in the EVs research field that focus on their roles in the aged and/or neurodegenerative brain. We particularly encourage the submission of original research, review articles, and reports covering recent developments, while other article types, such as papers describing significant methodological advances on EVs isolation and characterization, which remain a challenge, will also be considered. Submitted contributions may address, but are not limited to, the following topics:


• EVs formation, cargo loading, trafficking, and release in a physiological and pathological context.

• Intracellular mechanisms underlying EVs functions using in vitro/in vivo aging or neurodegenerative models.

• Advancements in therapeutic and diagnostic applications of EVs in brain disorders.

• Isolation and characterization methods of brain-cell-derived EVs.

Keywords: Extracellular vesicles, neurodegeneration, aging, biomarker, therapeutics


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Research into extracellular vesicles (EVs) biology has increased considerably over the past decade, posing manifold questions regarding their involvement in homeostatic and pathological processes. EVs are nano-sized particles and can be classified broadly into exosomes (40-150 nm), microvesicles (50-2000 nm), or apoptotic bodies (50-5000 nm). New classes of EVs also include smaller exomeres and supermeres (≤ 50 nm) and exophers, which vary widely in size from a ~1.5 μm diameter to the size of an entire cell. In the central nervous system (CNS), EVs are secreted by all cell types, including neurons and glia. EVs carry a cargo of nucleic acids, proteins, and lipids that varies, reflecting their cellular origin and the state of the originating cells. Following their release into the extracellular space, EVs can mediate intercellular communication, synaptic plasticity, antigen presentation, and neurotrophic support in the CNS.

Besides their crucial physiological roles, EVs are thought to propagate pathological age-related processes through miRNA regulation, neuroinflammation, the spread of toxic misfolded proteins, and possibly the spread of viruses. Interestingly, this spread may be mediated by EVs not only within the CNS but also between the CNS and peripheral tissues and organs. Moreover, alterations in EVs may be related to changes in in senescent cells and aging tissues, highlighting a putative role of EVs in the process of aging. At the same time, EVs are thought to contribute to the pathogenesis of various age-related neurodegenerative diseases (NDD), such as Alzheimer’s Disease and other tauopathies, Parkinson’s disease and other synucleinopathies, Huntington’s disease and other poly-glutamine related diseases, among others. However, the exact mechanisms that govern the role of EVs in the neurodegenerative context are not fully understood.

A better understanding of their formation, cargo loading, secretion, and uptake in inter- and intracellular neurogenerative pathways could shed light on the initiation and propagation mechanisms of various NDD, thereby contributing to the identification of effective therapeutic strategies. Notably, several properties of EVs, including the ability to cross the blood-brain barrier or the intimate relationship between their cargo and cell origin, make them excellent candidates for harboring biomarkers or drug delivery systems. Thus, contributing to the knowledge of the abovementioned mechanisms may further increase their potential as reliable diagnostic tools or advanced drug delivery systems to the brain in complex neurodegenerative conditions.

This Research Topic aims to present studies of the most recent developments in the EVs research field that focus on their roles in the aged and/or neurodegenerative brain. We particularly encourage the submission of original research, review articles, and reports covering recent developments, while other article types, such as papers describing significant methodological advances on EVs isolation and characterization, which remain a challenge, will also be considered. Submitted contributions may address, but are not limited to, the following topics:


• EVs formation, cargo loading, trafficking, and release in a physiological and pathological context.

• Intracellular mechanisms underlying EVs functions using in vitro/in vivo aging or neurodegenerative models.

• Advancements in therapeutic and diagnostic applications of EVs in brain disorders.

• Isolation and characterization methods of brain-cell-derived EVs.

Keywords: Extracellular vesicles, neurodegeneration, aging, biomarker, therapeutics


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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