A compound screen using zebrafish identified carbonic anhydrase (CA) as a modulator of tau toxicity. CA inhibition abrogates lysosomal acidification and causes tau secretion by lysosomal exocytosis without having a prion effect. This mechanism lowers intracellular tau and is neuroprotective in zebrafish and mouse models of tauopathy.
- Ana Lopez
- Farah H. Siddiqi
- David C. Rubinsztein