Detection of exosomal prions in blood by immunochemistry techniques

Properzi, Francesca; Logozzi, Mariantonia; Abdel‐Haq, Hanin; Federici, Cristina; Lugini, Luana; Azzarito, Tommaso; Cristofaro, Ilaria; Sevo, Daniela di; Ferroni, Elena; Cardone, Franco; Venditti, Massimo; Colone, Marisa; Comoy, Emmanuel; Durand, Valérie; Fais, Stefano; Pocchiari, Maurizio

doi:10.1099/vir.0.000117

Cited by 38 publications

(29 citation statements)

References 30 publications

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“…In addition, there is evidence that macrophages can phagocytose and translocate Aβ seeds (Eisele et al, 2014; Cintron et al, 2015). Small, cell-derived extracellular vesicles such as exosomes have been linked to the transmissibility of PrP-prions (Fevrier et al, 2004; Properzi et al, 2015; Guo et al, 2016a). Extracellular vesicles also have been suggested to ferry Aβ between cells (Rajendran et al, 2006), although their influence on the pathogenesis of AD – positive or negative - remains uncertain (Joshi et al, 2015).…”

Section: The Prion-like Properties Of Aggregated Aβmentioning

confidence: 99%

Prion-like mechanisms in Alzheimer disease

Walker

2018

Handbook of Clinical Neurology

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Senile plaques and neurofibrillary tangles are the principal histopathologic hallmarks of Alzheimer disease. The essential constituents of these lesions are structurally abnormal variants of normally generated proteins: Aβ protein in plaques and tau protein in tangles. At the molecular level, both proteins in a pathogenic state share key properties with classic prions, i.e., they consist of alternatively folded, β-sheet-rich forms of the proteins that autopropagate by the seeded corruption and self-assembly of like proteins. Other similarities with prions include the ability to manifest as polymorphic and polyfunctional strains, resistance to chemical and enzymatic destruction, and the ability to spread within the brain and from the periphery to the brain. In Alzheimer disease, current evidence indicates that the pathogenic cascade follows from the endogenous, sequential corruption of Aβ and then tau. Therapeutic options include reducing the production or multimerization of the proteins, uncoupling the Aβ-tauopathy connection, or promoting the inactivation or removal of anomalous assemblies from the brain. Although aberrant Aβ appears to be the prime mover of Alzheimer disease pathogenesis, once set in motion by Aβ, the prion-like propagation of tauopathy may proceed independently of Aβ; if so, Aβ might be solely targeted as an early preventive measure, but optimal treatment of Alzheimer disease at later stages of the cascade could require intervention in both pathways.

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Section: The Prion-like Properties Of Aggregated Aβmentioning

confidence: 99%

Prion-like mechanisms in Alzheimer disease

Walker

2018

Handbook of Clinical Neurology

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“…Both normal (PrP c ) and pathological (PrP sc ) prion proteins are incorporated into EVs by normal and prion-infected cells (51,52). PrP sc -carrying EVs are present in biological fluids (i.e., blood) of infected animals (53,54), and these PrP sc -carrying EVs can spread prion infection to normal recipient cells (55). These findings have opened up new and important insights into the complicated mechanisms of transmission and propagation of prion diseases.…”

Section: Evs In Physiology and Pathology Of The Nervous Systemmentioning

confidence: 99%

Extracellular vesicles and intercellular communication within the nervous system

Zappulli¹,

Friis²,

Fitzpatrick³

et al. 2016

Journal of Clinical Investigation

193

162

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“…We and others showed that prion-infected cultured cells actively secrete exosomes bearing misfolded PrP protein and prion infectivity [25][26][27][28][29][30][31]. Similarly, several pathological misfolded proteins like Tau, a-synuclein, SOD1, TDP-43 or the Ab peptide involved in the neurodegenerative diseases cited above were found to be released in association with exosomes, thus highlighting that a range of prion-like proteins with seeding activity may gain access to the extracellular space through their association with exosomes that can participate to their spreading [9,24,[32][33][34][35][36][37][38].…”

Section: Introductionmentioning

confidence: 99%

Efficient inhibition of infectious prions multiplication and release by targeting the exosomal pathway

Vilette

Laulagnier

Huor

et al. 2015

Cell. Mol. Life Sci.

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Exosomes are secreted membrane vesicles of endosomal origin present in biological fluids. Exosomes may serve as shuttles for amyloidogenic proteins, notably infectious prions, and may participate in their spreading in vivo. To explore the significance of the exosome pathway on prion infectivity and release, we investigated the role of the endosomal sorting complex required for transport (ESCRT) machinery and the need for ceramide, both involved in exosome biogenesis. Silencing of HRS-ESCRT-0 subunit drastically impairs the formation of cellular infectious prion due to an altered trafficking of cholesterol. Depletion of Tsg101-ESCRT-I subunit or impairment of the production of ceramide significantly strongly decreases infectious prion release. Together, our data reveal that ESCRT-dependent and -independent pathways can concomitantly regulate the exosomal secretion of infectious prion, showing that both pathways operate for the exosomal trafficking of a particular cargo. These data open up a new avenue to regulate prion release and propagation.

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Detection of exosomal prions in blood by immunochemistry techniques

Cited by 38 publications

References 30 publications

Prion-like mechanisms in Alzheimer disease

Prion-like mechanisms in Alzheimer disease

Extracellular vesicles and intercellular communication within the nervous system

Efficient inhibition of infectious prions multiplication and release by targeting the exosomal pathway

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