| Exosomal PrP C : spreading or trapping of neurotoxic proteins in neurodegeneration. Role in prion diseases (left): transport of PrP Sc via exosomes secreted from a prion-infected cell or binding of PrP Sc to exosomal PrP C may enhance transmission and spreading. Role in AD (right): capturing and detoxifying of neurotoxic Aß-peptides by exosomal PrP C may act neuroprotective. Aß-fibrils bound to exosomes may contribute to Aß plaque formation or may enable uptake and degradation by microglia.
Exosomes are involved in the progression ofneurodegenerative diseases. The cellular prion protein (PrPC) is highly expressed on exosomes. In neurodegenerative diseases, PrPC has at least two functions: It is the substrate for the generation of pathological prion protein (PrPSc), a key player in the pathophysiology of prion diseases. On the other h.
In recent years, exosomes have attracted considerable interest in the study of brain diseases, such as Alzheimer's disease, Parkinson's disease, stroke, and traumatic brain injury, due to their critical importance in the disease process and potential value for clinical application. The role and molecular mechanisms of exosomes carrying proteins related to the brain diseases [amyloid precursor protein (APP), α-synuclein (α-syn), mHtt, PrPsc] have been emphatically explored (Hartmann et al., 2017;Leblanc et al., 2017;Wang J. K. T. et al., 2017;Hill, 2019;Li B. et al., 2020;Pan et al., 2020;Perez-Gonzalez et al., 2020;Singh and Muqit, 2020;Tsunemi et al., 2020Tsunemi et al., , 2021Ananbeh et al., 2021;Soares Martins et al., 2021a). Notably, their ability to transport cargo is a key mechanism involved in the spread of disease. ...
... There is plenty of evidence that supports the intercellular transfer of prion proteins via exosomes (Cheng et al., 2018). Cellular prion protein (Prpc) regulates cell adhesion and signaling in the brain (Hartmann et al., 2017). Prpc binds to dynein, muskelin, and KIF5C in exosomes, while muskelin coordinates the bidirectional transport of Prpc between the extracellular space and lysosomes.
It is important to note that both PrP and α-Syn are transported via extracellular vesicles and exosomes which are highly enriched in RNA and perhaps can act as potential sites for such multiphasic interactions.  The interplay of these critical molecular events can have broad implications in physiologically relevant receptor-mediated signaling as well as in disease-associated aberrant phase transitions. 55 were used to predict the LLPS propensity of both PrP and α-Syn.