Rapid metabolic and bioenergetic adaptations of astrocytes under hyperammonemia - a novel perspective on hepatic encephalopathy

Marcel Zimmermann, Andreas S Reichert, Marcel Zimmermann, Andreas S Reichert

Abstract

Hepatic encephalopathy (HE) is a well-studied, neurological syndrome caused by liver dysfunctions. Ammonia, the major toxin during HE pathogenesis, impairs many cellular processes within astrocytes. Yet, the molecular mechanisms causing HE are not fully understood. Here we will recapitulate possible underlying mechanisms with a clear focus on studies revealing a link between altered energy metabolism and HE in cellular models and in vivo. The role of the mitochondrial glutamate dehydrogenase and its role in metabolic rewiring of the TCA cycle will be discussed. We propose an updated model of ammonia-induced toxicity that may also be exploited for therapeutic strategies in the future.

Keywords: TCA cycle; autophagy; glutamine metabolism; hepatic encephalopathy; hyperammonemia; mitochondrial dysfunction.

© 2021 Marcel Zimmermann and Andreas S. Reichert, published by De Gruyter, Berlin/Boston.

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