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• W3199103692 endingPage "105186" @default.
• W3199103692 startingPage "105186" @default.
• W3199103692 abstract "Recent genetic and molecular studies have indicated that the innate immune system, especially microglia, have a crucial role in the accumulation of β-amyloid plaques in Alzheimer's disease (AD). In particular, the CD33 receptor, also called Siglec-3, inhibits the TREM2 receptor-induced phagocytic activity of microglia. CD33 receptors recognize the α2,3 and α2,6-linked sialic groups in tissue glycocalyx, especially sialylated gangliosides in human brain. The CD33 receptor triggers cell-type specific responses, e.g., in microglia, CD33 inhibits phagocytosis, whereas in natural killer cells, it inhibits the cytotoxic activity of the NKG2D receptor. Nonetheless, the regulation of the activity of CD33 receptor needs to be clarified. For example, it seems that hypoxia/ischemia, a potential cause of AD pathology, increases the expression of CD33 and its downstream target SHP-1, a tyrosine phosphatase which suppresses the phagocytosis driven by TREM2. Moreover, hypoxia/ischemia increases the deposition of sialylated gangliosides, e.g., GM1, GM2, GM3, and GD1, which are ligands for inhibitory CD33/Siglec-3 receptors. In addition, β-amyloid peptides bind to the sialylated gangliosides in raft-like clusters and subsequently these gangliosides act as seeds for the formation of β-amyloid plaques in AD pathology. It is known that senile plaques contain sialylated GM1, GM2, and GM3 gangliosides, i.e., the same species induced by hypoxia/ischemia treatment. Sialylated gangliosides in plaques might stimulate the CD33/Siglec-3 receptors of microglia and thus impede TREM2-driven phagocytosis. We propose that hypoxia/ischemia, e.g., via the accumulation of sialylated gangliosides, prevents the phagocytosis of β-amyloid deposits by inhibiting CD33/TREM2 signaling." @default.
• W3199103692 created "2021-09-27" @default.
• W3199103692 creator A5021448617 @default.
• W3199103692 creator A5071846201 @default.
• W3199103692 creator A5080618425 @default.
• W3199103692 date "2021-11-01" @default.
• W3199103692 modified "2023-09-23" @default.
• W3199103692 title "Hypoxia/ischemia impairs CD33 (Siglec-3)/TREM2 signaling: Potential role in Alzheimer's pathogenesis" @default.
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