Abstract

Aging is consistently reported as the most important independent risk factor for neurodegenerative diseases. As life expectancy has significantly increased during the 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 (AD), Frontotemporal Dementia (FTD) and Parkinson disease (PD). The search for biomarkers has been focused so far on cerebrospinal fluid (CSF) and blood. Recently, exosomes emerged as novel biological source with increasing interest for age-related neurodegenerative disease biomarkers. Exosomes are tiny Extracellular vesicles (EVs; 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 (signaling, toxic, and regulatory) molecules among cells. Initially considered with merely waste disposal function, instead exosomes have been recently recognized as fundamental mediators of intercellular communication. They can move from the site of release 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.

Highlights

  • EXTRACELLULAR VESICLES (EVs)The growing increase of lifespan has implemented the research in aging processes and in age related pathologies like Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD) and Parkinson’s disease (PD)

  • Exosomes were thought to serve as cellular garbage but there are many evidence that support their role in the intercellular communication (Rashed et al, 2017) pouring their content, through different mechanisms, to the recipient cells in the neighborhood as well as in the periphery even passing through the blood brain barrier (BBB; Alvarez-Erviti et al, 2011; Ridder et al, 2014)

  • Exosome cargo consists of lipid, proteins, mRNAs and non-coding RNAs (ncRNAs), mostly microRNAs, whose sorting is regulated from the cell of origin with complex mechanisms that are not fully understood (Simons and Raposo, 2009)

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Summary

INTRODUCTION

The growing increase of lifespan has implemented the research in aging processes and in age related pathologies like Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD) and Parkinson’s disease (PD). Exosome cargo consists of lipid, proteins, mRNAs and ncRNAs, mostly microRNAs, whose sorting is regulated from the cell of origin with complex mechanisms that are not fully understood (Simons and Raposo, 2009). Instead, it is not clear, if the recipient cell can have an active role to select the exosome cargo or if it depends only from the parental cell. The biochemical content of exosomes consists of lipid, proteins and microRNA and mRNAs. Several studies reported that mRNAs delivered by exosomes to target cells were translated in functional proteins (Pegtel et al, 2010); in the same way miRNAs regulated gene expression in recipient cells (Figure 1; Hu et al, 2019). They appear potentially useful biomarkers for the diagnosis of several diseases, including neurodegenerative diseases

Exosomes in Aging and Cellular Senescence
The Role of Exosome miRNAs in Aging and Cellular Senescence
Findings
CONCLUDING REMARKS
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