Abstract
Growing evidence indicates that small extracellular vesicles, called exosomes, are prominent mediators of neurodegenerative diseases such as prion, Alzheimer’s and Parkinson’s disease. Exosomes contain neurodegenerative disease associated proteins such as the prion protein, β-amyloid and α-synuclein. Only demonstrated so far in vivo with prion disease, exosomes are hypothesised to also facilitate the spread of β-amyloid and α-synuclein from their cells of origin to the extracellular environment. In the current review, we will discuss the role of exosomes in Alzheimer’s and Parkinson’s disease including their possible contribution to disease propagation and pathology and highlight their utility as a diagnostic in neurodegenerative disease.
Highlights
Neurodegenerative diseases including Alzheimer’s, Parkinson’s and prion disease have distinct clinical manifestations and molecular pathology they share common features such as aggregation of disease specific proteins
Proteomic analysis of Parkinson’s disease (PD) patient sera derived exosomes performed on grouped samples of patients with genetic and sporadic forms of PD and healthy subjects identified 23 exosome-associated proteins that were differentially abundant in PD, including the regulator of exosome biogenesis syntenin 1 [76]
The deposited proteins act as a template to instigate further progression of the disease which spread throughout the brain
Summary
Neurodegenerative diseases including Alzheimer’s, Parkinson’s and prion disease have distinct clinical manifestations and molecular pathology they share common features such as aggregation of disease specific proteins. These include β-amyloid (Aβ) in Alzheimer’s disease (AD), α-synuclein (α-syn) in Parkinson’s disease (PD) and the prion protein (PrP) in prion disease. Cell-to-cell contact and passive spread were initially deemed responsible; more recently small extracellular vesicles, called exosomes, were proposed to play a role [3,4]. In the case of prion disease, exosomes alter recipient cell function by transmitting infectivity and initiating a cascade of events that further spreads and propagates the disease (for a review see [3]). We review the recent literature regarding the possible roles of exosomes in AD and PD and discuss their potential in biomarker discovery
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