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Allosteric regulation of pathologic angiogenesis: potential application for angiogenesis-related blindness

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Abstract

Angiogenesis-related blindness (ARB) includes age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, all of which are based on pathologic angiogenesis. Current treatment options such as surgery, laser photocoagulation, and steroid have shown limitations because they do not directly resolve the pathologic events in the retina. Furthermore, recently approved and developed therapeutic drugs only focus on direct inhibition of growth factors and suppression of downstream signaling molecules of activated receptor proteins by orthosteric ligands. In this regard, allosteric regulation of receptors and ligands can be a valuable mechanism in the development of novel drugs for ARB. In this review, we briefly address the clinical significance of ARB for further discussion on allosteric regulation of pathologic angiogenesis for ARB. Interestingly, key molecules in the pathogenesis of ARB can be targets for allosteric regulation, sharing characteristics as allosteric proteins. With investigation of allostery by introducing well-established models for allosteric proteins and currently published novel allosteric modulators, we discuss the potential of allosteric regulation for ARB. In conclusion, we hope that allosteric regulation of pathologic angiogenesis in ARB can open new opportunities for drug development.

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Acknowledgments

This study was supported by National Research Foundation (NRF) grant funded by the Korea government (MEST) (2012-0006019), the Seoul National University Research Grant (800-20130338), the Pioneer Research Program of NRF/MEST (2012-0009544), and the Bio-Signal Analysis Technology Innovation Program of NRF/MEST (2009-0090895).

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Authors and Affiliations

  1. Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, 110-744, Korea

    Dong Hyun Jo, Jin Hyoung Kim & Jeong Hun Kim

  2. Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 110-799, Korea

    Dong Hyun Jo & Jeong Hun Kim

  3. College of Pharmacy, Seoul National University, Seoul, 151-742, Korea

    Kyu-Won Kim & Young-Ger Suh

  4. Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, 110-744, Korea

    Jeong Hun Kim

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  1. Dong Hyun Jo
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  2. Jin Hyoung Kim
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  3. Kyu-Won Kim
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  5. Jeong Hun Kim
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Correspondence to Jeong Hun Kim.

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Jo, D.H., Kim, J.H., Kim, KW. et al. Allosteric regulation of pathologic angiogenesis: potential application for angiogenesis-related blindness. Arch. Pharm. Res. 37, 285–298 (2014). https://doi.org/10.1007/s12272-013-0324-y

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  • DOI: https://doi.org/10.1007/s12272-013-0324-y

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