颅神经损伤
-
Figure 1 (A) The pathological hallmarks of Parkinson’s disease (PD) are Lewy bodies, cytoplasmic inclusions leading to a degeneration of neurons. The main components of Lewy bodies are misfolded and aggregated α-synuclein protein, fragmented membranes, organelles, and vesicles. (B) Extracellular vesicles of neural origin can be isolated from peripheral blood and are a source of biomarkers for pathologies of the central nervous system like PD. Unpublished data.
We have recently described that oligomeric α-syn species are increased, whereas the SNARE components STX-1A and VAMP-2 are diminished in neural-derived extracellular vesicles (NDEVs) of PD patients (Agliardi et al., 2021), corroborating the hypothesis of a direct role for α-syn in the exocytosis of neurotransmitters. Under still unknown conditions, α-syn physiological conformations (monomeric species, dimers, and probably tetramers) undergo pathological aggregation (oligomers, fibrils) that subsequently degenerate into Lewy neuritis and Lewy bodies cytoplasmic inclusions, the hallmark of PD (Uversky, 2007) (Figure 1A).
Shi et al., in 2014, injected radiolabeled α-syn into mouse brain, demonstrated that CSF α-syn was transported to blood, and showed that a small proportion of CSF α-syn was contained in exosomes originating from neurons. They subsequently isolated exosomes from plasma samples of PD patients and HC using superparamagnetic microbeads coated with the neural cell adhesion molecule L1CAM and measured α-syn content. Results showed that plasma neural derived exosomes from PD patients contain higher levels of α-syn compared to HC and indicated that α-syn levels correlate with disease severity. Similar results were obtained by analyzing NDEVs isolated from plasma by precipitation with the polymer ExoQuick? (System Bioscience, CA, USA), subsequent incubation with a biotinylated L1CAM antibody, and selection using a streptavidin resin (Fiandaca et al., 2014) (Figure 1B).