Substances with therapeutic potential affecting the Keap1-Nrf2-ARE pathway in age-related eye diseases
One of the features of the uninterrupted progress of civilization, also in the field of medicine, is the extension of the average life length, which ultimately leads to the aging of societies in developed and developing countries. The disadvantage of this phenomenon is the higher appearance of age-r...
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| Format: | Article |
| Language: | Polish |
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Polish Pharmaceutical Society
2023-09-01
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| Series: | Farmacja Polska |
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| Online Access: | https://www.ptfarm.pl/download/?file=File%2FFarmacja+Polska%2F2023%2F4%2F06_SZ_Substancje_o_potencjale_terapeutycznym_.pdf |
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| author | Julia Sajak Kacper Wojnarowski BARBARA STRZAŁKA-MROZIK |
| author_facet | Julia Sajak Kacper Wojnarowski BARBARA STRZAŁKA-MROZIK |
| author_sort | Julia Sajak |
| collection | DOAJ |
| description | One of the features of the uninterrupted progress of civilization, also in the field of medicine, is the extension of the average life length, which ultimately leads to the aging of societies in developed and developing countries. The disadvantage of this phenomenon is the higher appearance of age-related diseases. These include, among others, eye diseases such as: cataracts, glaucoma, diabetic retinopathy or age-related macular degeneration, which are the most common reasons for the irreversible loss of vision among elderly people. However, age is not the only risk factor for developing these diseases. Among others, we can distinguish: lifestyle, use of stimulants such as alcohol, nicotine, exposure to UV radiation or accompanying diseases such as diabetes. However, a common factor in their development is oxidative stress, and the eye is an organ particularly sensitive to its effects. Especially the retina and the cells of the retinal pigment epithelium are exposed to an extremely high load of oxidative stress, which increases with age.
The human body has many antioxidant defences mechanisms, and one of them that plays an important role ,also in the antioxidant mechanisms of the eye, is the the Keap1-Nrf2-ARE signalling pathway.
Nrf2 is a nuclear transcription factor of erythroid origin, type 2, which is present in the cytosol in the form of a complex with its inhibitor, the Keap1 protein. Under normal, non-stress conditions, Nrf2 is destined for proteasomal degradation, but under oxidative stress it is dissociated and transduced into the cell nucleus. As a result, Nrf2 activates the expression of genes known as elements of the antioxidant response. They are responsible for the synthesis of phase II cytoprotective enzymes, which include: heme oxygenase 1, superoxide dismutase, glutathione S-transferase or γ-glutamyl cysteine ligase.
Due to the fact that oxidative stress is involved in the development of many diseases, signalling pathways that reduce its level may be a potential therapeutic target. Especially the multifaceted influence on the functioning of the Nrf2 factor as ubiquitous in the body and modifications of the Keap1-Nrf2-ARE signalling pathway seem to be a promising direction in the search for new forms of therapy, also in the case of age-related eye diseases.
Among the numerous substances with therapeutic potential that affect the activity of the Keap1-Nrf2-ARE pathway, plant-derived compounds such as lutein, zeaxanthin, polyphenols such as quercetin and resveratrol, and drugs such as probucol and calcium dobesylate should be mentioned. |
| first_indexed | 2024-03-08T18:55:42Z |
| format | Article |
| id | doaj.art-3eadfcdbc47a4928bd55c6722e45d459 |
| institution | Directory Open Access Journal |
| issn | 0014-8261 |
| language | Polish |
| last_indexed | 2024-03-08T18:55:42Z |
| publishDate | 2023-09-01 |
| publisher | Polish Pharmaceutical Society |
| record_format | Article |
| series | Farmacja Polska |
| spelling | doaj.art-3eadfcdbc47a4928bd55c6722e45d4592023-12-28T12:27:49ZpolPolish Pharmaceutical SocietyFarmacja Polska0014-82612023-09-0179423724810.32383/farmpol/171661171661Substances with therapeutic potential affecting the Keap1-Nrf2-ARE pathway in age-related eye diseasesJulia Sajak0https://orcid.org/0009-0009-2299-0889Kacper Wojnarowski1https://orcid.org/0009-0000-9552-6096BARBARA STRZAŁKA-MROZIK2https://orcid.org/0000-0001-9854-2569Zakład Biologii Molekularnej Katedry Biologii Molekularnej, Śląski Uniwersytet Medyczny w Katowicach, Wydział Nauk Farmaceutycznych w Sosnowcu, PolskaZakład Biologii Molekularnej Katedry Biologii Molekularnej, Wydział Nauk Farmaceutycznych w Sosnowcu, Śląski Uniwersytet Medyczny w Katowicach, PolskaZakład Biologii Molekularnej Katedry Biologii Molekularnej, Wydział Nauk Farmaceutycznych w Sosnowcu, Śląski Uniwersytet Medyczny w Katowicach, PolskaOne of the features of the uninterrupted progress of civilization, also in the field of medicine, is the extension of the average life length, which ultimately leads to the aging of societies in developed and developing countries. The disadvantage of this phenomenon is the higher appearance of age-related diseases. These include, among others, eye diseases such as: cataracts, glaucoma, diabetic retinopathy or age-related macular degeneration, which are the most common reasons for the irreversible loss of vision among elderly people. However, age is not the only risk factor for developing these diseases. Among others, we can distinguish: lifestyle, use of stimulants such as alcohol, nicotine, exposure to UV radiation or accompanying diseases such as diabetes. However, a common factor in their development is oxidative stress, and the eye is an organ particularly sensitive to its effects. Especially the retina and the cells of the retinal pigment epithelium are exposed to an extremely high load of oxidative stress, which increases with age. The human body has many antioxidant defences mechanisms, and one of them that plays an important role ,also in the antioxidant mechanisms of the eye, is the the Keap1-Nrf2-ARE signalling pathway. Nrf2 is a nuclear transcription factor of erythroid origin, type 2, which is present in the cytosol in the form of a complex with its inhibitor, the Keap1 protein. Under normal, non-stress conditions, Nrf2 is destined for proteasomal degradation, but under oxidative stress it is dissociated and transduced into the cell nucleus. As a result, Nrf2 activates the expression of genes known as elements of the antioxidant response. They are responsible for the synthesis of phase II cytoprotective enzymes, which include: heme oxygenase 1, superoxide dismutase, glutathione S-transferase or γ-glutamyl cysteine ligase. Due to the fact that oxidative stress is involved in the development of many diseases, signalling pathways that reduce its level may be a potential therapeutic target. Especially the multifaceted influence on the functioning of the Nrf2 factor as ubiquitous in the body and modifications of the Keap1-Nrf2-ARE signalling pathway seem to be a promising direction in the search for new forms of therapy, also in the case of age-related eye diseases. Among the numerous substances with therapeutic potential that affect the activity of the Keap1-Nrf2-ARE pathway, plant-derived compounds such as lutein, zeaxanthin, polyphenols such as quercetin and resveratrol, and drugs such as probucol and calcium dobesylate should be mentioned.https://www.ptfarm.pl/download/?file=File%2FFarmacja+Polska%2F2023%2F4%2F06_SZ_Substancje_o_potencjale_terapeutycznym_.pdfretinal pigment epitheliumoxidative stressnrf2-keap1-pathwayage-related eye diseases |
| spellingShingle | Julia Sajak Kacper Wojnarowski BARBARA STRZAŁKA-MROZIK Substances with therapeutic potential affecting the Keap1-Nrf2-ARE pathway in age-related eye diseases Farmacja Polska retinal pigment epithelium oxidative stress nrf2-keap1-pathway age-related eye diseases |
| title | Substances with therapeutic potential affecting the Keap1-Nrf2-ARE pathway in age-related eye diseases |
| title_full | Substances with therapeutic potential affecting the Keap1-Nrf2-ARE pathway in age-related eye diseases |
| title_fullStr | Substances with therapeutic potential affecting the Keap1-Nrf2-ARE pathway in age-related eye diseases |
| title_full_unstemmed | Substances with therapeutic potential affecting the Keap1-Nrf2-ARE pathway in age-related eye diseases |
| title_short | Substances with therapeutic potential affecting the Keap1-Nrf2-ARE pathway in age-related eye diseases |
| title_sort | substances with therapeutic potential affecting the keap1 nrf2 are pathway in age related eye diseases |
| topic | retinal pigment epithelium oxidative stress nrf2-keap1-pathway age-related eye diseases |
| url | https://www.ptfarm.pl/download/?file=File%2FFarmacja+Polska%2F2023%2F4%2F06_SZ_Substancje_o_potencjale_terapeutycznym_.pdf |
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