Abstract
Telomeric diseases are a group of rare progeroid genetic syndromes, presenting premature aging phenotypes, characterized for defects on telomere maintenance. In humans, telomeres are heterochromatic structures consisting of long TTAGGG repeats located at the chromosomal ends, which shorten progressively after each DNA replication because of the ‘end replication problem’. Critically short telomeres activate a DNA damage response that leads to the arrest of the cell cycle and resulting in cellular senescence or apoptosis. Furthermore, excessively short telomeres are prone to create telomeric fusions, causing genomic instability and malignant transformation. In order to counteract this process, there are two enzymatic complexes, the telomerase complex, with the capacity to elongate telomeres; and the shelterin complex, which protects them from being recognized as DNA breaks. Over the last few decades, several studies have confirmed that critically short telomeres and defects in telomere-associated enzymatic complexes are involved in the development of a group of rare human genetic diseases, with the accumulation of excessive telomere attrition as the underlying cause of these pathologies. Despite the severity of these disorders, there is no curative treatment for any of them. In light of this, this review summarizes the most important defective telomere diseases, their current management, and it presents possible therapeutic strategies based on nanotechnology which may open up new possibilities for their treatment.
Keywords: Drug delivery systems, genetic diseases, nanotechnology, premature aging, telomerase, telomere attrition/shortening.
Mini-Reviews in Medicinal Chemistry
Title:Emerging Therapeutic Approaches Based on Nanotechnology for the Treatment of Diseases Associated with Telomere Dysfunction
Volume: 15 Issue: 6
Author(s): Susana Patricia Egusquiaguirre, Jose Luis Pedraz, Rosa Maria Hernandez and Manuela Igartua
Affiliation:
Keywords: Drug delivery systems, genetic diseases, nanotechnology, premature aging, telomerase, telomere attrition/shortening.
Abstract: Telomeric diseases are a group of rare progeroid genetic syndromes, presenting premature aging phenotypes, characterized for defects on telomere maintenance. In humans, telomeres are heterochromatic structures consisting of long TTAGGG repeats located at the chromosomal ends, which shorten progressively after each DNA replication because of the ‘end replication problem’. Critically short telomeres activate a DNA damage response that leads to the arrest of the cell cycle and resulting in cellular senescence or apoptosis. Furthermore, excessively short telomeres are prone to create telomeric fusions, causing genomic instability and malignant transformation. In order to counteract this process, there are two enzymatic complexes, the telomerase complex, with the capacity to elongate telomeres; and the shelterin complex, which protects them from being recognized as DNA breaks. Over the last few decades, several studies have confirmed that critically short telomeres and defects in telomere-associated enzymatic complexes are involved in the development of a group of rare human genetic diseases, with the accumulation of excessive telomere attrition as the underlying cause of these pathologies. Despite the severity of these disorders, there is no curative treatment for any of them. In light of this, this review summarizes the most important defective telomere diseases, their current management, and it presents possible therapeutic strategies based on nanotechnology which may open up new possibilities for their treatment.
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Cite this article as:
Egusquiaguirre Patricia Susana, Pedraz Luis Jose, Hernandez Maria Rosa and Igartua Manuela, Emerging Therapeutic Approaches Based on Nanotechnology for the Treatment of Diseases Associated with Telomere Dysfunction, Mini-Reviews in Medicinal Chemistry 2015; 15 (6) . https://dx.doi.org/10.2174/1389557515666150226114522
DOI https://dx.doi.org/10.2174/1389557515666150226114522 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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