Affiliation: Porto Alegre
- ColÃn GonzÃ¡lez A, Paz Loyola A, Serratos I, Seminotti B, Ribeiro C, Leipnitz G, et al. The effect of WIN 55,212-2 suggests a cannabinoid-sensitive component in the early toxicity induced by organic acids accumulating in glutaric acidemia type I and in related disorders of propionate metabolism in rat brain synaptosomes. Neuroscience. 2015;310:578-88 pubmed publisher..Our findings support a protective and modulatory role of cannabinoids in the early toxic events elicited by toxic metabolites involved in OAs. ..
- Leipnitz G, Vargas C, Wajner M. Disturbance of redox homeostasis as a contributing underlying pathomechanism of brain and liver alterations in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. J Inherit Metab Dis. 2015;38:1021-8 pubmed publisher..In this review we focus on the deleterious effects of these carboxylic acids on redox homeostasis in rat and human tissues that may offer new perspectives for potential novel adjuvant therapeutic strategies in this disorder. ..
- Fernandes C, Rodrigues M, Seminotti B, Colín González A, Santamaria A, Quincozes Santos A, et al. Induction of a Proinflammatory Response in Cortical Astrocytes by the Major Metabolites Accumulating in HMG-CoA Lyase Deficiency: the Role of ERK Signaling Pathway in Cytokine Release. Mol Neurobiol. 2016;53:3586-3595 pubmed publisher..Taken together, the data indicate that the principal compounds accumulating in HMGA induce a proinflammatory response in cultured astrocytes that may possibly be involved in the neuropathology of this disease. ..
- Zanatta A, Rodrigues M, Amaral A, Souza D, Quincozes Santos A, Wajner M. Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome. Neurochem Res. 2016;41:2190-8 pubmed publisher..It is presumed that these mechanisms may be involved in the neuropathology of this disease. ..
- Amaral A, Cecatto C, da Silva J, Wajner A, Godoy K, Ribeiro R, et al. cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca(2+) homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency. Biochim Biophys Acta. 2016;1857:1363-1372 pubmed publisher
- Cecatto C, Godoy K, da Silva J, Amaral A, Wajner M. Disturbance of mitochondrial functions provoked by the major long-chain 3-hydroxylated fatty acids accumulating in MTP and LCHAD deficiencies in skeletal muscle. Toxicol In Vitro. 2016;36:1-9 pubmed publisher..It is proposed that these pathomechanisms disrupting mitochondrial homeostasis may be involved in the muscle alterations characteristic of MTP and LCHAD deficiencies. ..
- Rodrigues M, Seminotti B, Zanatta A, de Mello Gonçalves A, Bellaver B, Amaral A, et al. Higher Vulnerability of Menadione-Exposed Cortical Astrocytes of Glutaryl-CoA Dehydrogenase Deficient Mice to Oxidative Stress, Mitochondrial Dysfunction, and Cell Death: Implications for the Neurodegeneration in Glutaric Aciduria Type I. Mol Neurobiol. 2017;54:4795-4805 pubmed publisher..It is presumed that these pathomechanisms may contribute to the cortical leukodystrophy observed in GA-I patients. ..
- Cecatto C, Amaral A, da Silva J, Wajner A, Godoy K, Ribeiro R, et al. Mevalonolactone disrupts mitochondrial functions and induces permeability transition pore opening in rat brain mitochondria: Implications for the pathogenesis of mevalonic aciduria. Neurochem Int. 2017;108:133-145 pubmed publisher..It is therefore presumed that disturbance of brain mitochondrial homeostasis possibly contributes to the neurologic symptoms in MVA. ..
- da Silva J, Amaral A, Cecatto C, Wajner A, Dos Santos Godoy K, Ribeiro R, et al. Î±-Ketoadipic Acid and Î±-Aminoadipic Acid Cause Disturbance of Glutamatergic Neurotransmission and Induction of Oxidative Stress In Vitro in Brain of Adolescent Rats. Neurotox Res. 2017;32:276-290 pubmed publisher..We speculate that disturbance of glutamatergic neurotransmission and redox homeostasis by KAA and AAA may play a role in those cases of Î±-ketoadipic aciduria that display neurological symptoms. ..
- Seminotti B, Amaral A, Ribeiro R, Rodrigues M, Colín González A, Leipnitz G, et al. Oxidative Stress, Disrupted Energy Metabolism, and Altered Signaling Pathways in Glutaryl-CoA Dehydrogenase Knockout Mice: Potential Implications of Quinolinic Acid Toxicity in the Neuropathology of Glutaric Acidemia Type I. Mol Neurobiol. 2016;53:6459-6475 pubmed publisher..Therefore, it is presumed that QUIN may possibly contribute to the pathophysiology of striatal degeneration in children with glutaric aciduria type I during inflammatory processes triggered by infections or vaccinations. ..
- Rodrigues M, Seminotti B, Amaral A, Leipnitz G, GOODMAN S, Woontner M, et al. Experimental evidence that overexpression of NR2B glutamate receptor subunit is associated with brain vacuolation in adult glutaryl-CoA dehydrogenase deficient mice: A potential role for glutamatergic-induced excitotoxicity in GA I neuropathology. J Neurol Sci. 2015;359:133-40 pubmed publisher..These data indicate higher susceptibility of Gcdh(-/-) mice to excitotoxic damage, implying that this pathomechanism may contribute to the cortical and striatum alterations observed in GA I patients. ..
- Pierozan P, Colín González A, Biasibetti H, da Silva J, Wyse A, Wajner M, et al. Toxic Synergism Between Quinolinic Acid and Glutaric Acid in Neuronal Cells Is Mediated by Oxidative Stress: Insights to a New Toxic Model. Mol Neurobiol. 2018;55:5362-5376 pubmed publisher..Therefore, it is likely that oxidative stress may play a major causative role in the synergistic actions exerted by QUIN + GA in a variety of cell culture conditions involving the interaction of different neural types. ..
- Zanatta A, Cecatto C, Ribeiro R, Amaral A, Wyse A, Leipnitz G, et al. S-Adenosylmethionine Promotes Oxidative Stress and Decreases Na+, K+-ATPase Activity in Cerebral Cortex Supernatants of Adolescent Rats: Implications for the Pathogenesis of S-Adenosylhomocysteine Hydrolase Deficiency. Mol Neurobiol. 2018;55:5868-5878 pubmed publisher..Finally, reduction of Na+, K+-ATPase activity provoked by AdoMet may lead to impaired neurotransmission, but disturbance of this system should be better clarified in future studies. ..
- Amaral A, Seminotti B, da Silva J, de Oliveira F, Ribeiro R, Vargas C, et al. Induction of Neuroinflammatory Response and Histopathological Alterations Caused by Quinolinic Acid Administration in the Striatum of Glutaryl-CoA Dehydrogenase Deficient Mice. Neurotox Res. 2018;33:593-606 pubmed publisher..The present data indicate that QA significantly contributes to the histopathological changes observed in the striatum of Gcdh-/- mice. ..