Arrazola Sastre, A.; Luque Montoro, M.; Llavero, F.; Zugaza, J.L. Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration. Cells2023, 12, 1876.
Arrazola Sastre, A.; Luque Montoro, M.; Llavero, F.; Zugaza, J.L. Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration. Cells 2023, 12, 1876.
Arrazola Sastre, A.; Luque Montoro, M.; Llavero, F.; Zugaza, J.L. Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration. Cells2023, 12, 1876.
Arrazola Sastre, A.; Luque Montoro, M.; Llavero, F.; Zugaza, J.L. Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration. Cells 2023, 12, 1876.
Abstract
Protein O-GlcNAcylation has been associated with neurodegenerative diseases such as Alzheimer´s disease (AD). O-GlcNAcylation of Amyloid Precursor Protein (APP) regulates both the trafficking and the processing of the APP through the amyloidogenic pathway, resulting in the release and aggregation of the Aβ1-42 peptide. Microglia clear Aβ aggregates and dead cells to maintain brain homeostasis. Here, using LC-MS/MS we reveal that the Aβ1-42 peptide modifies the microglia O-GlcNAcome. We have identified 55 proteins, focusing our research on Galectin-1 protein, since it is a very versatile protein from a functional point of view. Combining biochemical with genetic approaches we demonstrate that Aβ1-42 peptide specifically targets Galectin-1S8 O-GlcNAcylation via OGT. In addition, this Gal-1-O-GlcNAcylated form, in turn, controls human microglia migration. Given the importance of microglia migration in the progression of AD, this study reports the relationship between Aβ1-42 peptide and Serine 8- O-GlcNAcylation of Galectin to drive microglial migration
Biology and Life Sciences, Neuroscience and Neurology
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