Ataxin-2 loss flips a metabolic switch for neuron health.

Lowering ataxin-2 protects neurons from TDP-43 toxicity in amyotrophic lateral sclerosis by activating neuronal glycolysis and astrocytic cholesterol synthesis.

• Why it matters: The work addresses how ataxin-2 loss can improve neuron health in ALS despite TDP-43–linked molecular pathology remaining largely unchanged.
• What they did: Gastaldo et al. 1 tested whether ataxin-2 lowering alters TDP-43-dependent pathology, and mapped metabolic changes to neuronal glycolysis and astrocytic cholesterol synthesis.
• The result: The findings indicate the protective effect is linked to metabolic activation rather than reversal of TDP-43-dependent molecular pathology, highlighting IDH1 and HMGCS1 as candidate therapeutic targets.

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