A metabolic key to protecting the brain from tauopathy
New research reveals a protective role for astrocytic glycogen metabolism in a mouse model of tauopathy, a neurodegenerative disease characterized by toxic tau protein accumulation. The study found that expression of the glycogenolytic enzyme PYGM increases in the brains of patients with a related disorder and in tau-transgenic mice. Deleting PYGM specifically in astrocytes worsened cognitive deficits and tau-related pathology in mice, while overexpressing it or supplementing with lactate, a key metabolic product, had protective effects. The findings suggest that astrocytes support neuronal health by breaking down glycogen into lactate, and that enhancing this metabolic pathway could be a therapeutic strategy for tauopathies.
Why it might matter to you:
This work shifts focus from neurons to the supporting role of astrocytes in neurodegenerative disease, highlighting metabolic coupling as a critical mechanism. For a researcher in neurodevelopmental disorders, it underscores the importance of investigating non-neuronal cell types and brain energy metabolism as potential contributors to pathology or targets for intervention. The study provides a mechanistic framework that could be explored in the context of developmental disruptions to glial function.
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