Abstract
Extracellular vesicles (EVs) are involved in the development and progression of neurodegenerative diseases, including Alzheimer's and Parkinson's disease. Moreover, EVs have the capacity to modify the physiology of neuronal circuits by transferring proteins, RNA, lipids, and metabolites. The proteomic characterization of EVs (exosomes and microvesicles) from preclinical models and patient samples has the potential to reveal new proteins and molecular networks that affect the normal physiology prior to the appearance of traditional biomarkers of neurodegeneration. Noteworthy, many of the genetic risks associated to the development of Alzheimer's and Parkinson's disease affect the crosstalk between mitochondria, endosomes, and lysosomes. Recent research has focused on determining the role of endolysosomal trafficking in the onset of neurodegenerative diseases. Proteomic studies indicate an alteration of biogenesis and molecular content of EVs as a result of endolysosomal and autophagic dysfunction. In this review, we discuss the status of EV proteomic characterization and their usefulness in discovering new biomarkers for the differential diagnosis of neurodegenerative diseases. Despite the challenges related to the failure to follow a standard isolation protocol and their implementation for a clinical setting, the analysis of EV proteomes has revealed the presence of key proteins with post-translational modifications that can be measured in peripheral fluids.
Highlights
Neurodegenerative diseases (NDs) are complex disorders with devastating consequences for the patient and their immediate social environment
While epileptic status selectively modifies the miRNA content of hippocampus-derived Extracellular vesicles (EVs), it does not modify the process of miRNA editing that occurs inside the vesicle, which modulates target recognition [24]. These findings suggest that the information contained in the EVs add an extra layer of modulation for normal synaptic functioning, which can be bidirectional among neurons
The brainderived EVs from 3xTgAD mouse (APP Swedish mutation, Tau P301L, and Presenilin 1 M146V) or from neuroblastoma cells show an accumulation of amyloid precursor protein (APP)-C-terminal fragments (CTFs) induced by the inhibition of the γ-secretase, a molecular complex involved in Aβ peptide generation
Summary
Neurodegenerative diseases (NDs) are complex disorders with devastating consequences for the patient and their immediate social environment. The molecular characterization of EVs is promising because the analysis in both patient samples and disease models may reflect the type of molecules that are expressed at different stages of the development of NDs. Interestingly, it has been described that brain-derived exosomes can be found in peripheral circulation.
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