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- Title
Experimental evidence of tyrosine neurotoxicity: focus on mitochondrial dysfunction.
- Authors
de Oliveira, Jade; Farias, Hémelin Resende; Streck, Emilio Luiz
- Abstract
Tissue exposure to high levels of tyrosine, which is characteristic of an inborn error of metabolism named Tyrosinemia, is related to severe symptoms, including neurological alterations. The clinical manifestations and pathogenesis of tyrosine neurotoxicity can be recapitulated in experimental models in vivo and in vitro. A widely used experimental model to study brain tyrosine damage is the chronic and acute administration of this amino acid in infant rats. Other research groups and we have extensively studied the pathogenic events in the brain structures of rats exposed to high tyrosine levels. Rats administered acutely and chronically with tyrosine presented decreased and inhibition of the essential metabolism enzymes, e.g., Krebs cycle enzymes and mitochondrial respiratory complexes in the brain structures. These alterations induced by tyrosine toxicity were associated with brain oxidative stress, astrocytes, and, ultimately, cognitive impairments. Notably, in vivo data were corroborated by in vitro studies using cerebral regions homogenates incubated with tyrosine excess. Considering metabolism's importance to brain functioning, we hypothesized that mitochondrial and metabolic dysfunctions are closely related to neurological alterations induced by tyrosine neurotoxicity. Herein, we reviewed the main mechanisms associated with tyrosine neurotoxicity in experimental models, emphasizing the role of mitochondrial dysfunction.
- Subjects
TYROSINE; BRAIN anatomy; INBORN errors of metabolism; NEUROTOXICOLOGY; KREBS cycle
- Publication
Metabolic Brain Disease, 2021, Vol 36, Issue 7, p1673
- ISSN
0885-7490
- Publication type
Article
- DOI
10.1007/s11011-021-00781-w