Exogenous l-fucose attenuates neuroinflammation induced by lipopolysaccharide

Xu, Xing; Fukuda, Tomohiko; Takai, Jun; Morii, Sayaka; Sun, Yuhan; Liu, Jianwei; Ohno, Shiho; Isaji, Tomoya; Yamaguchi, Yoshiki; Nakano, Miyako; Moriguchi, Takashi; Gu, Jianguo

doi:10.1016/j.jbc.2023.105513

Cited by 4 publications

(1 citation statement)

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“…Additionally, proinflammatory cytokine expression is increased when human IPSC microglia are exposed to LPS and oligomeric amyloid beta leading to comparable increases in specific forms of glycosylation including fucosylation of glycoconjugates [ 67 ]. Conversely, specific modifications of l ‐fucosylation of glycans on the cell surface of microglia attenuate LPS stimulation of proinflammatory cytokine release [ 68 ]. Thus, there are unique changes in microglia glycosylation states based on stimuli and model, highlighting the need to better understand specific changes in SA function within in vivo models.…”

Section: Discussionmentioning

confidence: 99%

Distinct patterns of plaque and microglia glycosylation in Alzheimer's disease

Fastenau,

Bunce,

Keating

et al. 2024

Brain Pathology

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Glycosylation is the most common form of post‐translational modification in the brain. Aberrant glycosylation has been observed in cerebrospinal fluid and brain tissue of Alzheimer's disease (AD) cases, including dysregulation of terminal sialic acid (SA) modifications. While alterations in sialylation have been identified in AD, the localization of SA modifications on cellular or aggregate‐associated glycans is largely unknown because of limited spatial resolution of commonly utilized methods. The present study aims to overcome these limitations with novel combinations of histologic techniques to characterize the sialylation landscape of O‐ and N‐linked glycans in autopsy‐confirmed AD post‐mortem brain tissue. Sialylated glycans facilitate important cellular functions including cell‐to‐cell interaction, cell migration, cell adhesion, immune regulation, and membrane excitability. Previous studies have not investigated both N‐ and O‐linked sialylated glycans in neurodegeneration. In this study, the location and distribution of sialylated glycans were evaluated in three brain regions (frontal cortex, hippocampus, and cerebellum) from 10 AD cases using quantitative digital pathology techniques. Notably, we found significantly greater N‐sialylation of the Aβ plaque microenvironment compared with O‐sialylation. Plaque‐associated microglia displayed the most intense N‐sialylation proximal to plaque pathology. Further analyses revealed distinct differences in the levels of N‐ and O‐sialylation between cored and diffuse Aβ plaque morphologies. Interestingly, phosphorylated tau pathology led to a slight increase in N‐sialylation and no influence of O‐sialylation in these AD brains. Confirming our previous observations in mice with novel histologic approach, these findings support microglia sialylation appears to have a relationship with AD protein aggregates while providing potential targets for therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%