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Advanced Neurology Proteomic analysis of microglia exosomes

levels due to post-transcriptional and post-translational deleterious process. After observing the different impacts
regulation. Therefore, elucidating the disparities in protein of exosomes, we performed proteomic studies to compare
expression within exosomes is highly important. Paracrine and analyze the differences in exosomal proteins derived
signaling through exosomes is widely acknowledged as from microglia of different phenotypes.
a pivotal mechanism through which MSCs exert their In the present study, 1129 proteins were quantified and
therapeutic effects. Comparative proteomics studies have characterized. The GO analysis revealed that M1-EXO
revealed that exosomes derived from umbilical cord MSCs proteins are involved in the inflammatory response,
excel in tissue damage repair, bone marrow MSC-derived neutrophil chemotaxis, and complement activation,
exosomes enhance regenerative potential, and adipose while M2-EXO proteins predominantly participate in
MSC-derived exosomes are primarily involved in immune protein transport and cellular proliferation. Furthermore,
regulation. These findings lay a robust foundation for M2-EXOs negatively regulate chemotaxis and extrinsic
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guiding future stem cell research endeavors. Consequently, apoptotic signals. The findings from the KEGG analysis
our ongoing research aims to characterize differences in agreed with those of the GO analysis, indicating that
exosomal proteins among microglial phenotypes (M0, exosome proteins originating from M1 microglia primarily
M1, and M2). By investigating these disparities, we seek engage in complement, apoptosis, and inflammation
to gain valuable insights for advancing future fundamental pathways, whereas exosomal proteins from M2 microglia
research on the role of microglia in various neurological are associated with glucose metabolism and the MAPK
diseases. signaling pathway governing cell proliferation.

Little is known about the impact of microglial exosomes In the subsequent study, we first performed a
on neuronal apoptosis following ischemia. A study revealed PPI analysis to observe the interplay among DEPs.
that exosomes from the LPS-activated BV2 microglial cell Subsequently, we analyzed several proteins of interest that
line induce apoptosis in PC12 neuronal cells. Interestingly, occupy a central position within the PPI network. Based on
deleting the TNF-inducing protein 3 gene in BV2 cells their established functions, these proteins can be divided
exacerbated this process. In the same year, another into proinflammatory, chemotactic, complement system,
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study demonstrated that IL-4-activated BV2 cells, which and phagocytosis-related categories. Our findings revealed
transition to the M2 phenotype, release exosomal miR-124 significant variations in the expression levels of the
that mitigates ischemic brain injury and neuronal death. inflammation-associated proteins IL-6 and SAA3 across
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Despite these investigations, the lack of correlation between distinct groups, with a marked increase in M1-EXOs and
their underlying mechanisms hampers a comprehensive a decrease in M2-EXOs. A study highlighted the ability
understanding of the intrinsic role of microglial exosomes of IL-6 to be detected in plasma exosomes from patients
in neuronal apoptosis. with multiple types of trauma, in contrast to the inability
Recently, Juliet et al. investigated the differences to detect IL-1β and TNF-α, even with highly sensitive
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in exosomes released by the microglial cell line BV2 in ELISAs. This finding is consistent with our results,
response to different stimuli. Next, they focused on the indicating that the proinflammatory factor IL-6 can be
effects of LPS-induced exosomes released by BV2 cells transmitted between cells through exosomes. Although
on resting BV2 cells, but not neurons. These LPS-induced earlier research has shown that SAA3 can promote the
exosomes increased the expression of proinflammatory proinflammatory response and influence the phenotypic
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genes in resting microglia. However, researchers have polarization of microglia, recent studies have shown
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suggested that BV2 cells only partially replicate primary that microglia can secrete SAA3. Our data suggest the
microglial behavior. Therefore, we exposed primary presence of SAA3 in microglial exosomes, opening a novel
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microglia to LPS and IL-4, which induce two distinct avenue for investigating the role of SAA3 in ischemic brain
microglial phenotypes, to elucidate the microglial exosomal injury in the future.
proteins involved in modulating neuronal apoptosis Neutrophils are the first peripheral immune cells
post-ischemia. Then, we isolated and characterized the to infiltrate the brain after an ischemic stroke. After
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morphology, dimensions, and integrity of the exosomes entering the cerebral infarct area, neutrophils can
released by these microglia. These results align with the aggravate brain injury by forming neutrophil extracellular
literature, thus satisfying the prerequisites for further traps. Moreover, neutrophil infiltration is governed by
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investigations. Our findings revealed that exosomes various chemotactic molecules released by microglia.
derived from M1 microglia exacerbated ischemia-induced Recent studies have reported that numerous chemotactic
neuronal apoptosis both in vivo and in vitro, whereas molecules are present in exosomes. Our findings suggest
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exosomes from M2 microglia notably ameliorated this a notable abundance of CCL5 and CCL9 within M1-EXOs,

Volume 3 Issue 3 (2024) 11 doi: 10.36922/an.3166