Publicação
Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration
| Resumo: | Age-related macular degeneration (AMD) is the leading cause of vision loss in the Western world, and it currently lacks effective therapy. It is believed that AMD initiates in the aged retinal pigment epithelium (RPE), which presents lysosomal dysfunction and oxidative stress (OxS) that ultimately leads to RPE damage and AMD progression. AMD is a complex pathology, so multitarget treatments are required to act on different pathways, presenting several challenges. In this review, we discuss the current knowledge on the pathogenesis of this disease, focusing mainly on lysosomal dysfunction and OxS. Because transcription factors regulate homeostasis, the transcription factor EB (TFEB), which controls lysosomal function and biogenesis, and the nuclear factor erythroid 2-related factor 2 (NRF2), which manages OxS, have been proposed as promising targets for disease intervention. Finally, we discuss the interplay of these pathways for a potential synergistic effect on AMD-targeted therapies, as they could change the course of today’s available treatments for AMD. |
|---|---|
| Autores principais: | Falcão, Ana S. |
| Outros Autores: | AS, Falcão; Pedro, Margarida L.; Tenreiro, Sandra; Tenreiro, Sandra; Seabra, Miguel C.; C Seabra, Miguel |
| Assunto: | age-related macular degeneration lysosomal dysfunction NRF2 oxidative stress retinal pigment epithelium TFEB/mTORC1 axis Food Science Physiology Biochemistry Molecular Biology Clinical Biochemistry Cell Biology |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | recensão |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1868983681647902720 |
|---|---|
| author | Falcão, Ana S. |
| author2 | AS, Falcão Pedro, Margarida L. Tenreiro, Sandra Tenreiro, Sandra Seabra, Miguel C. C Seabra, Miguel |
| author2_role | author author author author author author |
| author_facet | Falcão, Ana S. AS, Falcão Pedro, Margarida L. Tenreiro, Sandra Tenreiro, Sandra Seabra, Miguel C. C Seabra, Miguel |
| author_role | author |
| contributor_name_str_mv | iNOVA4Health - pólo NMS NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) MDPI - Multidisciplinary Digital Publishing Institute RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Falcão, Ana S.\"},{\"Person.name\":\"AS, Falcão\",\"Person.identifier.orcid\":\"0000-0002-4491-7457\"},{\"Person.name\":\"Pedro, Margarida L.\"},{\"Person.name\":\"Tenreiro, Sandra\"},{\"Person.name\":\"Tenreiro, Sandra\",\"Person.identifier.orcid\":\"0000-0001-7272-5842\"},{\"Person.name\":\"Seabra, Miguel C.\"},{\"Person.name\":\"C Seabra, Miguel\",\"Person.identifier.orcid\":\"0000-0002-6404-4892\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | iNOVA4Health - pólo NMS NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) MDPI - Multidisciplinary Digital Publishing Institute RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Falcão, Ana S. AS, Falcão Pedro, Margarida L. Tenreiro, Sandra Tenreiro, Sandra Seabra, Miguel C. C Seabra, Miguel |
| datacite.date.Accepted.fl_str_mv | 2025-05-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2025-07-01T21:17:46Z |
| datacite.date.embargoed.fl_str_mv | 2025-07-01T21:17:46Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | age-related macular degeneration lysosomal dysfunction NRF2 oxidative stress retinal pigment epithelium TFEB/mTORC1 axis Food Science Physiology Biochemistry Molecular Biology Clinical Biochemistry Cell Biology |
| datacite.titles.title.fl_str_mv | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| dc.contributor.none.fl_str_mv | iNOVA4Health - pólo NMS NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) MDPI - Multidisciplinary Digital Publishing Institute RUN |
| dc.creator.none.fl_str_mv | Falcão, Ana S. AS, Falcão Pedro, Margarida L. Tenreiro, Sandra Tenreiro, Sandra Seabra, Miguel C. C Seabra, Miguel |
| dc.date.Accepted.fl_str_mv | 2025-05-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2025-07-01T21:17:46Z |
| dc.date.embargoed.fl_str_mv | 2025-07-01T21:17:46Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/184706 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | age-related macular degeneration lysosomal dysfunction NRF2 oxidative stress retinal pigment epithelium TFEB/mTORC1 axis Food Science Physiology Biochemistry Molecular Biology Clinical Biochemistry Cell Biology |
| dc.title.fl_str_mv | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_efa0 |
| description | Age-related macular degeneration (AMD) is the leading cause of vision loss in the Western world, and it currently lacks effective therapy. It is believed that AMD initiates in the aged retinal pigment epithelium (RPE), which presents lysosomal dysfunction and oxidative stress (OxS) that ultimately leads to RPE damage and AMD progression. AMD is a complex pathology, so multitarget treatments are required to act on different pathways, presenting several challenges. In this review, we discuss the current knowledge on the pathogenesis of this disease, focusing mainly on lysosomal dysfunction and OxS. Because transcription factors regulate homeostasis, the transcription factor EB (TFEB), which controls lysosomal function and biogenesis, and the nuclear factor erythroid 2-related factor 2 (NRF2), which manages OxS, have been proposed as promising targets for disease intervention. Finally, we discuss the interplay of these pathways for a potential synergistic effect on AMD-targeted therapies, as they could change the course of today’s available treatments for AMD. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | review |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/fd5005ad-6735-45c5-a33d-f8c7475c0383/download |
| id | run_198f719f94deae86b4951549c8484911 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/184706 |
| inst_facet_str | urn:organizationAcronym:unl{{{_:::_}}}Universidade Nova de Lisboa |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/184706 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Falcão, Ana S. AS, Falcão AS, Falcão https://www.ciencia-id.pt/EC17-1F25-9969 EC17-1F25-9969 http://orcid.org/0000-0002-4491-7457 0000-0002-4491-7457 Pedro, Margarida L. Tenreiro, Sandra Tenreiro, Sandra Tenreiro, Sandra https://www.ciencia-id.pt/2214-5455-2764 2214-5455-2764 http://orcid.org/0000-0001-7272-5842 0000-0001-7272-5842 Seabra, Miguel C. C Seabra, Miguel C Seabra, Miguel https://www.ciencia-id.pt/2512-FAEF-E26F 2512-FAEF-E26F http://orcid.org/0000-0002-6404-4892 0000-0002-6404-4892 |
| publishDate | 2025 |
| repo_facet_str | urn:repositoryAcronym:run{{{_:::_}}}Repositório Institucional da UNL |
| reponame_str | Repositório Institucional da UNL |
| repository_id_str | urn:repositoryAcronym:run |
| service_str_mv | urn:repositoryAcronym:run |
| spelling | engenAge-related macular degeneration (AMD) is the leading cause of vision loss in the Western world, and it currently lacks effective therapy. It is believed that AMD initiates in the aged retinal pigment epithelium (RPE), which presents lysosomal dysfunction and oxidative stress (OxS) that ultimately leads to RPE damage and AMD progression. AMD is a complex pathology, so multitarget treatments are required to act on different pathways, presenting several challenges. In this review, we discuss the current knowledge on the pathogenesis of this disease, focusing mainly on lysosomal dysfunction and OxS. Because transcription factors regulate homeostasis, the transcription factor EB (TFEB), which controls lysosomal function and biogenesis, and the nuclear factor erythroid 2-related factor 2 (NRF2), which manages OxS, have been proposed as promising targets for disease intervention. Finally, we discuss the interplay of these pathways for a potential synergistic effect on AMD-targeted therapies, as they could change the course of today’s available treatments for AMD.application/pdfenTargeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular DegenerationFalcão, Ana S.PersonalAS, FalcãoDSpacehttp://dspace.org/items/7baf07a3-9ea7-4765-bf51-88caf9163a5cDSpacehttp://dspace.org/items/7baf07a3-9ea7-4765-bf51-88caf9163a5cFalcãoAnaCiência IDhttps://www.ciencia-id.ptEC17-1F25-9969ORCIDhttp://orcid.org0000-0002-4491-7457Researcher IDhttps://www.researcherid.comM-5600-2013Scopus Author IDhttps://www.scopus.com8896201400Pedro, Margarida L.Tenreiro, SandraPersonalTenreiro, SandraDSpacehttp://dspace.org/items/69a3db58-3303-47a3-a7bb-b19d9ba8c36aDSpacehttp://dspace.org/items/69a3db58-3303-47a3-a7bb-b19d9ba8c36aTenreiroSandraCiência IDhttps://www.ciencia-id.pt2214-5455-2764ORCIDhttp://orcid.org0000-0001-7272-5842Researcher IDhttps://www.researcherid.comA-9289-2013Scopus Author IDhttps://www.scopus.com6602925840Seabra, Miguel C.PersonalC Seabra, MiguelDSpacehttp://dspace.org/items/d6eeb095-df2d-4fd0-8241-ab826e5ecb1dDSpacehttp://dspace.org/items/d6eeb095-df2d-4fd0-8241-ab826e5ecb1dSeabraMiguelCiência IDhttps://www.ciencia-id.pt2512-FAEF-E26FORCIDhttp://orcid.org0000-0002-6404-4892Researcher IDhttps://www.researcherid.comM-3280-2013Scopus Author IDhttps://www.scopus.com7004369652iNOVA4Health - pólo NMSNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)MDPI - Multidisciplinary Digital Publishing InstituteHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf2076-3921URNIsPartOfPURE: 118628312URNIsPartOfPURE UUID: cb901666-2d72-4d18-a843-7f2cf711616bURNIsPartOfScopus: 105007651012DOIIsPartOf10.3390/antiox140505962025-07-01T21:17:46Z2025-052025-05-01T00:00:00ZHandlehttp://hdl.handle.net/10362/184706http://purl.org/coar/access_right/c_abf2open accessage-related macular degenerationlysosomal dysfunctionNRF2oxidative stressretinal pigment epitheliumTFEB/mTORC1 axisFood SciencePhysiologyBiochemistryMolecular BiologyClinical BiochemistryCell Biology2078779 bytesother research producthttp://purl.org/coar/resource_type/c_efa0reviewhttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/fd5005ad-6735-45c5-a33d-f8c7475c0383/download |
| spellingShingle | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration Falcão, Ana S. age-related macular degeneration lysosomal dysfunction NRF2 oxidative stress retinal pigment epithelium TFEB/mTORC1 axis Food Science Physiology Biochemistry Molecular Biology Clinical Biochemistry Cell Biology |
| status | SINGLETON |
| subject.fl_str_mv | age-related macular degeneration lysosomal dysfunction NRF2 oxidative stress retinal pigment epithelium TFEB/mTORC1 axis Food Science Physiology Biochemistry Molecular Biology Clinical Biochemistry Cell Biology |
| title | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| title_full | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| title_fullStr | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| title_full_unstemmed | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| title_short | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| title_sort | Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration |
| topic | age-related macular degeneration lysosomal dysfunction NRF2 oxidative stress retinal pigment epithelium TFEB/mTORC1 axis Food Science Physiology Biochemistry Molecular Biology Clinical Biochemistry Cell Biology |
| topic_facet | age-related macular degeneration lysosomal dysfunction NRF2 oxidative stress retinal pigment epithelium TFEB/mTORC1 axis Food Science Physiology Biochemistry Molecular Biology Clinical Biochemistry Cell Biology |
| url | http://hdl.handle.net/10362/184706 |
| visible | 1 |