Role of sulfated glycans in Alzheimer's!

Role of sulfated glycans in Alzheimer's!

The glycan molecule keratan sulfate (KS), which is found in microglia, has been implicated in amyotrophic lateral sclerosis, a neurodegenerative disorder that affects nerve cells in the brain and spinal cord. However, the functional roles of KS and the enzyme that synthesizes it, GlcNAc6ST1, in neurodegenerative disorders, such as Alzheimer’s disease (AD), remain unclear.

Researchers found that levels of KS and GlcNAc6ST1 were upregulated in the brains of two transgenic mouse models, including J20 mice, a model of AD, and in postmortem brain samples from AD patients.

Subsequently, the authors crossbred GlcNAc6ST1-deficient (GlcNAc6ST1−/−) mice with J20 mice. In primary microglial cells isolated from the resulting J20/GlcNAc6ST1−/− mice, the authors failed to find KS, but report correspondingly increased levels of amyloid β (Aβ) phagocytosis and a hyperactive response to IL-4, a potent antiinflammatory cytokine.

Moreover, the J20/GlcNAc6ST1−/− mice exhibited reduced levels of cerebral Aβ plaques. The findings suggest that GlcNAc6ST1 might regulate microglial function.

According to the authors, inhibition of KS synthesis by targeting GlcNAc6ST1 might provide a therapeutic approach for mitigating AD pathogenesis.