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Ar, Silva; Ruschel, Carla Felippi Chiella; Helegda, C.; Am, Brusque; Cm, Wannmacher; Wajner, Moaçir; Cs, Dustra-Filho

doi:10.1023/a:1020658624567

Cited by 11 publications

(4 citation statements)

References 34 publications

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“…Interestingly, GHB has been shown to inhibit lipid biosynthesis and to induce oxidative stress in rats [63,64]. Silva and colleagues suggested that altered lipid amounts were not caused by a direct inhibition of the enzymes involved in lipid biosynthesis by GHB, whereas mitochondria were likely to contribute to this effect [64]. These findings again point to the importance of indirect toxic effects in the disease pathogenesis of SSADH-D.…”

Section: Mitochondrial Dysfunction Redox Imbalance and Autophagy Dementioning

confidence: 99%

“…However, indirect effects that result in organelle dysfunction or impairment of signaling have been suggested to contribute to SSADH-D. For example, oxidative damage has been shown to be a prominent feature in both patients and in the murine SSADH-D model, and mitochondrial aberrations are frequently observed ( [62] and reviewed in [37]). Interestingly, GHB has been shown to inhibit lipid biosynthesis and to induce oxidative stress in rats [63,64]. Silva and colleagues suggested that altered lipid amounts were not caused by a direct inhibition of the enzymes involved in lipid biosynthesis by GHB, whereas mitochondria were likely to contribute to this effect [64].…”

Section: Mitochondrial Dysfunction Redox Imbalance and Autophagy Dementioning

confidence: 99%

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Succinic Semialdehyde Dehydrogenase Deficiency: An Update

Didiášová

Banning

Brennenstuhl

et al. 2020

Cells

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Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degrees of mental retardation, autism, ataxia, and epileptic seizures, but the clinical picture is highly heterogeneous. So far, there is no approved curative therapy for this disease. In this review, we briefly summarize the molecular genetics of SSADH-D, the past and ongoing clinical trials, and the emerging features of the molecular pathogenesis, including redox imbalance and mitochondrial dysfunction. The main aim of this review is to discuss the potential of further therapy approaches that have so far not been tested in SSADH-D, such as pharmacological chaperones, read-through drugs, and gene therapy. Special attention will also be paid to elucidating the role of patient advocacy organizations in facilitating research and in the communication between researchers and patients.

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Section: Mitochondrial Dysfunction Redox Imbalance and Autophagy Dementioning

confidence: 99%

Section: Mitochondrial Dysfunction Redox Imbalance and Autophagy Dementioning

confidence: 99%

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

Didiášová

Banning

Brennenstuhl

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Interestingly, GHB has been shown to inhibit lipid biosynthesis and to induce oxidative stress in rats [48,49]. Silva and colleagues suggested that altered lipid amounts were not caused by a direct inhibition of the enzymes involved in lipid biosynthesis by GHB, whereas mitochondria were likely to contribute to this effect [49]. These findings again point to the importance of indirect toxic effects in the disease pathogenesis of SSADH-D.…”

Section: Mitochondrial Dysfuntion Redox Imbalance and Autophagy Defementioning

confidence: 99%

“…However, indirect effects that result in organelle dysfunction or impairment of signaling have been suggested to contribute to SSADH-D. For example, oxidative damage has been shown to be a prominent feature in both patients and in the murine SSADH-D model, and mitochondrial aberrations are frequently observed ( [47] and reviewed in [30]). Interestingly, GHB has been shown to inhibit lipid biosynthesis and to induce oxidative stress in rats [48,49]. Silva and colleagues suggested that altered lipid amounts were not caused by a direct inhibition of the enzymes involved in lipid biosynthesis by GHB, whereas mitochondria were likely to contribute to this effect [49].…”

Section: Mitochondrial Dysfuntion Redox Imbalance and Autophagy Defementioning

confidence: 99%

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

Didiášová¹,

Banning²,

Brennenstuhl³

et al. 2020

Preprint

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Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by the impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degree of mental retardation, autism, ataxia and epileptic seizures, but the clinical picture is highly heterogeneous. So far, there is no approved therapy for this disease. In this review, we briefly summarize the molecular genetics of SSADH-D, the past and ongoing clinical trials and the emerging features of the molecular pathogenesis, including redox imbalance and mitochondrial dysfunction. The main aim of this review is to discuss the potential use of further therapy approaches that have so far not been tested in SSADH-D, such as pharmacological chaperones, read-through drugs and gene therapy. Special attention will also be paid to elucidating the role of patient advocacy organizations in facilitating research and in the communication between the researchers and the patients.

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Inhibition of energy productionin vitro by glutaric acid in cerebral cortex of young rats

Silva

Ruschel

et al. 2000

Metab Brain Dis

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The present study investigated the effects of glutaric acid (GA), which predominantly accumulates in glutaric acidemia type I (GA-I), on some in vitro parameters of energy metabolism in cerebral cortex of rats. We first evaluated CO2 production from [U-14C] acetate, as well as ATP levels in brain of young Wistar rats. The effect of the acid on the activities of the respiratory chain complexes were also investigated. GA was tested at final concentrations ranging from 0.5 to 5.0 mM. GA significantly reduced brain CO2 production by 50% at the concentrations of 0.5 to 3.0 mM, ATP levels by 25% at the concentration of 3.0 mM, succinate:cytochrome C oxireductase (complex II plus CoQ plus complex III) by 25% at 5 mM concentration, and NADH:cytochrome C oxireductase (complex I plus CoQ plus complex Ill) by 25% at 2.5 and 5 mM concentrations. The results strongly indicate that GA impairs brain energy production. If these effects also occur in humans, it is possible that they may contribute to the neuropathology of patients affected by GA-I.

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Untitled

Cited by 11 publications

References 34 publications

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

Inhibition of energy productionin vitro by glutaric acid in cerebral cortex of young rats

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