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Front. Aging Neurosci. | doi: 10.3389/fnagi.2019.00232

Exosome determinants of physiological aging and age related neurodegenerative diseases

 Marianna D'anca1, 2,  Chiara Fenoglio1, 2*, Maria Serpente1, 2,  Beatrice Arosio3, Matteo Cesari3, 4, Elio A. Scarpini2, 4, 5 and  Daniela Galimberti2, 4, 5
  • 1Department of Pathophysiology and Transplantation, Faculty of Medicine and Surgery, University of Milan, Italy
  • 2Dino Ferrari Center, University of Milan, Italy
  • 3Department of Clinical and Community Sciences, Faculty of Medicine and Surgery, University of Milan, Italy
  • 4IRCCS Ca 'Granda Foundation Maggiore Policlinico Hospital, Italy
  • 5Department of Biomedical, Surgical and Dental Sciences, Faculty of Medicine and Surgery, University of Milan, Italy

Aging is consistently reported as the most important independent risk factor for neurodegenerative diseases. As life expectancy has significantly increased during last decades, neurodegenerative diseases became one of the most critical public health problem in our society. The most investigated neurodegenerative diseases during aging are Alzheimer disease, Frontotemporal dementia and Parkinson disease. The search for biomarkers has been focused so far on cerebrospinal fluid and blood. Recently, exosomes emerged as novel biological source with increasing interest for age related neurodegenerative disease biomarkers.
Exosomes are small extracellular vesicles (30-100 nm in size) released by all cell types which originate from the endosomal compartment. They constitute important vesicles for the release and transfer of multiple (signalling, toxic, and regulatory) molecules among cells. Initially thought to have a function merely in waste disposal, exosomes have been recently recognized as fundamental mediators of intercellular communication. They can move from the site of discharge by diffusion and be retrieved in several body fluids, where they may dynamically reflect pathological changes of cells present in inaccessible sites such as the brain.
Multiple evidence has implicated exosomes in age-associated neurodegenerative processes, which lead to cognitive impairment in later life. Critically, consolidated evidence indicates that pathological protein aggregates, including Aβ, tau, and α-synuclein are released from brain cells in association with exosomes. Importantly, exosomes act as vehicles between cells not only of proteins but also of nucleic acids (DNA, mRNA transcripts, miRNA, and non-coding RNAs (ncRNAs) thus potentially influencing gene expression in target cells.
In this framework, exosomes could contribute to elucidate the molecular mechanisms underneath neurodegenerative diseases and could represent a promising source of biomarkers.
Despite the involvement of exosomes in age-associated neurodegeneration, the study of exosomes and their genetic cargo in physiological aging and in neurodegenerative diseases is still in its infancy. Here we review the current knowledge on protein and ncRNAs cargo of exosomes in normal aging and in age related neurodegenerative diseases.

Keywords: Exosomes, Aging, Alzheimer's disease, neurodegeneration, Frontotemporal deementia

Received: 18 Apr 2019; Accepted: 13 Aug 2019.

Edited by:

Gjumrakch Aliev, GALLY International Biomedical Research, United States

Reviewed by:

Fatah Kashanchi, George Mason University, United States
Safikur Rahman, Yeungnam University, South Korea  

Copyright: © 2019 D'anca, Fenoglio, Serpente, Arosio, Cesari, Scarpini and Galimberti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Chiara Fenoglio, Department of Pathophysiology and Transplantation, Faculty of Medicine and Surgery, University of Milan, Milan, 20122, Lombardy, Italy, chiara.fenoglio@unimi.it