Excitatory neurons downregulate synaptic proteins before motor onset and glia reduce neuronal support in Huntington disease mice

In R6/1 Huntington disease mice, cortical and hippocampal excitatory neurons downregulate synaptic proteins before motor onset, and this loss is not restored at later ages.

• Why it matters: Whole-tissue proteomes mix neurons and glia, obscuring how each cell type’s protein homeostasis shifts across disease progression and brain regions.
• What they did: Using cell-type-specific metabolic labeling in living R6/1 mice and wild-type littermates for 15 days, the authors profiled neurons and glia by mass spectrometry across 1.5, 3, and 7 months (plus glia at 7 months).
• The result: Neuronal UPS proteins increased as disease advanced, while synaptic proteins decreased early in cortical and hippocampal excitatory neurons without later recovery, implying coordinated functional reprogramming rather than uniform whole-tissue changes.

AI summary of the abstract · may contain errors · not medical advice · read the paper.