α-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging

Shrader, William D.; Amagata, Akiko; Barnes, Adam; Enns, Gregory M.; Hinman, A. Scott; Jankowski, Orion D.; Kheifets, Viktoria; Komatsuzaki, Ryo; Lee, Edgar; Mollard, Paul; Murase, Katsuyuki; Sadun, Alfredo A.; Thoolen, Martin; Wesson, Kieron E.; Miller, Guy

doi:10.1016/j.bmcl.2011.04.085

Cited by 86 publications

(66 citation statements)

References 62 publications

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“…It works by targeting an enzyme NADPH quinone oxidoreductase 1 (NQO1). Its mode of action is to synchronize energy generation in mitochondria with the need to counter cellular redox stress [149].…”

Section: Possible Targets For Pharmaceutical Interferencementioning

confidence: 99%

Genetic and Epigenetic Mechanisms in Down Syndrome Brain

Lu¹,

Sheen²

2013

Down Syndrome

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Section: Possible Targets For Pharmaceutical Interferencementioning

confidence: 99%

Genetic and Epigenetic Mechanisms in Down Syndrome Brain

Lu¹,

Sheen²

2013

Down Syndrome

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“…2A). CoQ10 and α-lipoic acid are clinically used in patients with mitochondrial diseases to attempt to enhance electron transfer within the respiratory chain (Pfeffer et al 2012), but these compounds had no effect on cell viability, as reported (Shrader et al 2011). On the other hand, compounds #2, #4, MA-5, #21 and #35 did exert a cell-protective effect ( Fig.…”

Section: Ma-5 Rescues Fibroblasts From Patients With Mitochondrial DImentioning

confidence: 99%

“…Quinones such as CoQ10 and idebenone are used as antioxidants to neutralize free radicals (Shrader et al 2011). To examine the redox properties of MA-5, we recorded cyclic voltammograms.…”

Section: Ma-5 Mediates a Novel Mechanism For Sustentationmentioning

confidence: 99%

“…BSO causes the decrease in cellular glutathione (GSH) and the increase in reactive ROS production, thereby inducing a variety of apoptotic signals (Shrader et al 2011).…”

Section: Ma-5 Rescues Fibroblasts From Patients With Mitochondrial DImentioning

confidence: 99%

“…Cyclic voltammograms were obtained for 0.5 mM CoQ10, 0.5 mM idebenone, 0.5 mM IAA and 0.5 mM MA-5 in an acetic acid/ acetonitrile mixture (4:1 by volume) containing 0.01 M sodium acetate as the supporting electrolyte, using a BASi C3 electrochemical analyzer, as previously reported (Shrader et al 2011). Cyclic voltammograms were recorded in a glass cell using a glassy carbon disk electrode (3 mm in diameter) as the working electrode, a platinum wire as the counter electrode and an Ag/Ag + electrode as the reference electrode.…”

Section: Recording Of Cyclic Voltammogrammentioning

confidence: 99%

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Mitochonic Acid 5 (MA-5), a Derivative of the Plant Hormone Indole-3-Acetic Acid, Improves Survival of Fibroblasts from Patients with Mitochondrial Diseases

Suzuki

Yamaguchi

Kikusato

et al. 2015

Tohoku J. Exp. Med.

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Mitochondria are key organelles implicated in a variety of processes related to energy and free radical generation, the regulation of apoptosis, and various signaling pathways. Mitochondrial dysfunction increases cellular oxidative stress and depletes ATP in a variety of inherited mitochondrial diseases and also in many other metabolic and neurodegenerative diseases. Mitochondrial diseases are characterized by the dysfunction of the mitochondrial respiratory chain, caused by mutations in the genes encoded by either nuclear DNA or mitochondrial DNA. We have hypothesized that chemicals that increase the cellular ATP levels may ameliorate the mitochondrial dysfunction seen in mitochondrial diseases. To search for the potential drugs for mitochondrial diseases, we screened an in-house chemical library of indole-3-acetic-acid analogs by measuring the cellular ATP levels in Hep3B human hepatocellular carcinoma cells. We have thus identified mitochonic acid 5 (MA-5), 4-(2,4-difluorophenyl)-2-(1H-indol-3-yl)-4-oxobutanoic acid, as a potential drug for enhancing ATP production. MA-5 is a newly synthesized derivative of the plant hormone, T. Suzuki et al. 226

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Effect of EPI-743 on the Clinical Course of the Mitochondrial Disease Leber Hereditary Optic Neuropathy

et al. 2012

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To evaluate the safety and efficacy of a new therapeutic agent, EPI-743, in Leber hereditary optic neuropathy (LHON) using standard clinical, anatomic, and functional visual outcome measures. Design: Open-label clinical trial. Setting: University medical center. Patients: Five patients with genetically confirmed LHON with acute loss of vision were consecutively enrolled and treated with the experimental therapeutic agent EPI-743 within 90 days of conversion. Intervention: During the course of the study, 5 consecutive patients received EPI-743, by mouth, 3 times daily (100-400 mg per dose). Main Outcome Measures: Treatment effect was assessed by serial measurements of anatomic and functional visual indices over 6 to 18 months, including Snellen visual acuity, retinal nerve fiber layer thickness measured by optical coherence tomography, Humphrey visual fields (mean decibels and area with 1-log unit depression), and color vision. Treatment effect in this clinical proof of principle study was assessed by comparison of the prospective open-label treatment group with historical controls. Results: Of 5 subjects treated with EPI-743, 4 demonstrated arrest of disease progression and reversal of visual loss. Two patients exhibited a total recovery of visual acuity. No drug-related adverse events were recorded. Conclusions: In a small open-label trial, EPI-743 arrested disease progression and reversed vision loss in all but 1 of the 5 consecutively treated patients with LHON. Given the known natural history of acute and rapid progression of LHON resulting in chronic and persistent bilateral blindness, these data suggest that the previously described irreversible priming to retinal ganglion cell loss may be reversed.

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α-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging

Cited by 86 publications

References 62 publications

Genetic and Epigenetic Mechanisms in Down Syndrome Brain

Genetic and Epigenetic Mechanisms in Down Syndrome Brain

Mitochonic Acid 5 (MA-5), a Derivative of the Plant Hormone Indole-3-Acetic Acid, Improves Survival of Fibroblasts from Patients with Mitochondrial Diseases

Effect of EPI-743 on the Clinical Course of the Mitochondrial Disease Leber Hereditary Optic Neuropathy

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