Ataxin-2 loss flips a metabolic switch for neuron health

Gastaldo et al. 1 1. Gastaldo, D. ∙ Vito, S. ∙ Black, H.H. ... Ataxin-2 downregulation rewires neuronal and astrocytic metabolism to protect against TDP-43 toxicity Cell Rep. 2026; 45 , 118053 Full Text Full Text (PDF) Scopus (0) PubMed Google Scholar report that lowering ataxin-2 protects neurons from TDP-43 toxicity in amyotrophic lateral sclerosis by activating neuronal glycolysis and astrocytic cholesterol synthesis, not by reversing TDP-43-dependent molecular pathology. The downstream effectors, IDH1 and HMGCS1, thus emerge as candidate therapeutic targets.