Neurotoxic Effects of<i>trans</i>-Glutaconic Acid in Rats

Schuck, Patrícia Fernanda; Busanello, Estela Natacha Brandt; Tonin, Anelise Miotti; Viegas, Carolina Maso; Ferreira, Gustavo C.

doi:10.1155/2013/607610

Cited by 2 publications

(1 citation statement)

References 62 publications

(53 reference statements)

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“…Koeller and colleagues [27] showed alterations of the expression of genes involved in mitochondrial energy metabolism and transport in cerebral cortex from a knock out mouse model. Many studies reported that GA, and 3-HGA elicit bioenergetics dysfunction both in vivo and in vitro, while tGA did not affect mitochondrial metabolism [28]. GA and 3HGA showed an inhibitory effect on complexes of mitochondrial respiratory chain in rat brain and chick embryonic neurons [29][30][31].…”

Section: Glutaric Acidemia Type Imentioning

confidence: 96%

Metabolic Disturbances in Diseases with Neurological Involvement

et al. 2014

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Degeneration of specific neuronal populations and progressive nervous system dysfunction characterize neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. These findings are also reported in inherited diseases such as phenylketonuria and glutaric aciduria type I. The involvement of mitochondrial dysfunction in these diseases was reported, elicited by genetic alterations, exogenous toxins or buildup of toxic metabolites. In this review we shall discuss some metabolic alterations related to the pathophysiology of diseases with neurological involvement and aging process. These findings may help identifying early disease biomarkers and lead to more effective therapies to improve the quality of life of the patients affected by these devastating illnesses.

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Section: Glutaric Acidemia Type Imentioning

confidence: 96%

Metabolic Disturbances in Diseases with Neurological Involvement

et al. 2014

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Genetically Predicted Higher Levels of Caffeic Acid Are Protective Against Ulcerative Colitis: A Comprehensive Metabolome Analysis

Naito,

Osaka,

Kakuta

et al. 2024

Inflammatory Bowel Diseases

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Background It is crucial to pinpoint the metabolites that cause Crohn’s disease (CD) and ulcerative colitis (UC) to comprehend their pathogenesis and identify possible targets for therapy. To achieve this goal, we performed the first metabolome-wide Mendelian randomization (MR) study of Japanese patients with CD and UC. Methods As exposure datasets, genetic instruments with blood-circulating metabolites were obtained from the Tohoku Medical Megabank Organization, which includes 204 metabolites from the genome-wide association study data of 7843 Japanese individuals. As outcome datasets, we enrolled Japanese patients with CD (n = 1803), Japanese patients with UC (n = 1992), and healthy controls (n = 2022). The main analysis utilized the inverse variance–weighted method, while stability of the findings was evaluated through sensitivity analyses. Results After single nucleotide polymorphism (SNP) filtering, 169 SNPs for 45 metabolites were available for MR. Genetically predicted elevated circulating trans-glutaconic acid and tryptophan were associated with a lower CD risk (odds ratio [OR], 0.68; P = 5.95 × 10−3; and OR, 0.64; P = 1.90 × 10−2, respectively). Genetically predicted elevated caffeic acid was associated with a lower UC risk (OR, 0.67; P = 4.2 × 10−4), which remained significant after multiple testing correction. We identified a causal link between UC and 3-hydroxybutyrate (OR, 2.21; P = 1.41 × 10−2), trans-glutaconic acid (OR, 0.72; P = 1.77 × 10−2), and 2-hydroxyvaleric acid (OR, 1.31; P = 4.23 × 10−2). There was no evidence of pleiotropy or reverse causal effects for these candidate metabolites. Conclusions In our metabolome-wide MR study, we discovered a notable protective effect of caffeic acid against UC.

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Neurotoxic Effects oftrans-Glutaconic Acid in Rats

Cited by 2 publications

References 62 publications

Metabolic Disturbances in Diseases with Neurological Involvement

Metabolic Disturbances in Diseases with Neurological Involvement

Genetically Predicted Higher Levels of Caffeic Acid Are Protective Against Ulcerative Colitis: A Comprehensive Metabolome Analysis

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