Integrated Approaches to Drug Discovery for Oxidative Stress‐Related Retinal Diseases

Nishimura, Yuhei; Hara, Hideaki

doi:10.1155/2016/2370252

Cited by 12 publications

(4 citation statements)

References 103 publications

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“…As for idebenone, the complete range of VitE functions is not completely uncovered. There is vast evidence that demonstrates the role of vitamin E in preventing oxidative stress, mainly in mitochondria of high oxygen consuming tissues as brain [6] and retina [68]. In recent years, novel functions of α-tocopherol have been discovered, and VitE seems to be involved in signaling cascades and gene regulation.…”

Section: Main Families Of Antioxidants Compoundsmentioning

confidence: 99%

Anti-Oxidant Drugs: Novelties and Clinical Implications in Cerebellar Ataxias

Barca

Emmanuele

DiMauro

et al. 2018

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Background:Hereditary cerebellar ataxias are a group of disorders characterized by heterogeneous clinical manifestations, progressive clinical course, and diverse genetic causes. No disease modifying treatments are yet available for many of these disorders. Oxidative stress has been recurrently identified in different progressive cerebellar diseases, and it represents a widely investigated target for treatment. Objective: To review the main aspects and new perspectives of antioxidant therapy in cerebellar ataxias ranging from bench to bedside. Method: This article is a summary of the state-of-the-art on the use of antioxidant molecules in cerebellar ataxia treatments. It also briefly summarizes aspects of oxidative stress production and general characteristics of antioxidant compounds. Results: Antioxidants represent a vast category of compounds; old drugs have been extensively studied and modified in order to achieve better biological effects. Despite the vast body of literature present on the use of antioxidants in cerebellar ataxias, for the majority of these disorders conclusive results on the efficacy are still missing.Conclusion:Antioxidant therapy in cerebellar ataxias is a promising field of investigations. To achieve the success in identifying the correct treatment more work needs to be done. In particular, a combined effort is needed by basic scientists in developing more efficient molecules, and by clinical researchers together with patients communities, to run clinical trials in order to identify conclusive treatments strategies.

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Section: Main Families Of Antioxidants Compoundsmentioning

confidence: 99%

Anti-Oxidant Drugs: Novelties and Clinical Implications in Cerebellar Ataxias

Barca

Emmanuele

DiMauro

et al. 2018

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“…High throughput screening of chemicals using in vitro and/or in vivo systems has also strongly driven DR ( Nishimura and Hara, 2016 ; Imamura et al, 2017 ). The sharing of chemicals among researchers with various assay systems can increase the success rate of DR, as demonstrated by the success of projects supported by the National Center for Advancing Translational Sciences in the US ( Azvolinsky, 2017 ).…”

Section: Future Directionsmentioning

confidence: 99%

Overcoming Obstacles to Drug Repositioning in Japan

et al. 2017

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Drug repositioning (DR) is the process of identifying new indications for existing drugs. DR usually focuses on drugs that have cleared phase-I safety trials but has yet to show efficacy for the intended indication. Therefore, DR can probably skip the preclinical and phase-I study, which can reduce the cost throughout drug development. However, the expensive phase-II/III trials are required to establish efficacy. The obstacles to DR include identification of new indications with a high success rate in clinical studies, obtaining funding for clinical studies, patent protection, and approval systems. To tackle these obstacles, various approaches have been applied to DR worldwide. In this perspective, we provide representative examples of DR and discuss the ongoing efforts to overcome obstacles to DR in Japan.

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“…This is of interest, for the retina has high oxygen consumption. In addition, given that the retina is constantly converting light into neural signals (Eshaq et al ., ), ROS are consequently produced from endogenous sources (Bhatt et al ., ; Kim et al ., ; Nishimura & Hara, ).…”

Section: Introductionmentioning

confidence: 98%

Pro‐survival redox signalling in progesterone‐mediated retinal neuroprotection

Lopez

Roche

Jackson

et al. 2017

Eur J of Neuroscience

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Retinitis pigmentosa (RP) is a group of hereditary retinal diseases, characterised by photoreceptor cell loss. Despite a substantial understanding of the mechanisms leading to cell death, an effective therapeutic strategy is sought. Our laboratory has previously demonstrated the neuroprotective properties of Norgestrel, a progesterone analogue, in the degenerating retina, mediated in part by the neurotrophic factor basic fibroblast growth factor (bFGF). In other retinal studies, we have also presented a pro‐survival role for reactive oxygen species (ROS), downstream of bFGF. Thus, we hypothesized that Norgestrel utilises bFGF‐driven ROS production to promote photoreceptor survival. Using the 661W photoreceptor‐like cell line, we now show that Norgestrel, working through progesterone receptor membrane complex 1 (PGRMC1); generates an early burst of pro‐survival bFGF‐induced ROS. Using the rd10 mouse model of RP, we confirm that Norgestrel induces a similar early pro‐survival increase in retinal ROS. Norgestrel‐driven protection in the rd10 retina was attenuated in the presence of antioxidants. This study therefore presents an essential role for ROS signalling in Norgestrel‐mediated neuroprotection in vitro and demonstrates that Norgestrel employs a similar pro‐survival mechanism in the degenerating retina.

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Integrated Approaches to Drug Discovery for Oxidative Stress‐Related Retinal Diseases

Cited by 12 publications

References 103 publications

Anti-Oxidant Drugs: Novelties and Clinical Implications in Cerebellar Ataxias

Anti-Oxidant Drugs: Novelties and Clinical Implications in Cerebellar Ataxias

Overcoming Obstacles to Drug Repositioning in Japan

Pro‐survival redox signalling in progesterone‐mediated retinal neuroprotection

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