Enhancing protein O-GlcNAcylation in down syndrome mice mitigates memory dysfunctions through the rescue of mitochondrial bioenergetics, stress responses and pathological markers.

ABSTRACT: Disturbances of the single sugar modification of proteins, O-GlcNAc, have been identified as a potential connection between disrupted brain metabolism and intellectual decay. In Alzheimer disease (AD), the reduced uptake of glucose in the brain results in aberrant O-GlcNAc cycling contributing to redox imbalance and neurodegeneration. Notably, alterations of O-GlcNAc homeostasis, associated with impaired O-GlcNAc transferase (OGT)/O-GlcNAcase (OGA) regulation, foster neuropathological mechanisms characterized by the presence of AD hallmarks in Down syndrome (DS) models. In the present study we examined the ability of Thiamet G (TMG), a well-known OGA inhibitor, in improving bio-energetic processes, inducing stress responses, reducing AD-related signatures and ameliorating cognition in a mu

SUBMITTER: Lanzillotta C 

PROVIDER: S-EPMC12301976 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature