Research Models to Study Ferroptosis’s Impact in Neurodegenerative Diseases
Ferroptosis is a type of regulated cell death promoted by the appearance of oxidative perturbations in the intracellular microenvironment constitutively controlled by glutathione peroxidase 4 (GPX4). It is characterized by increased production of reactive oxygen species, intracellular iron accumulat...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/5/1369 |
| _version_ | 1797598657220968448 |
|---|---|
| author | Inês Costa Daniel José Barbosa Vera Silva Sofia Benfeito Fernanda Borges Fernando Remião Renata Silva |
| author_facet | Inês Costa Daniel José Barbosa Vera Silva Sofia Benfeito Fernanda Borges Fernando Remião Renata Silva |
| author_sort | Inês Costa |
| collection | DOAJ |
| description | Ferroptosis is a type of regulated cell death promoted by the appearance of oxidative perturbations in the intracellular microenvironment constitutively controlled by glutathione peroxidase 4 (GPX4). It is characterized by increased production of reactive oxygen species, intracellular iron accumulation, lipid peroxidation, inhibition of system Xc-, glutathione depletion, and decreased GPX4 activity. Several pieces of evidence support the involvement of ferroptosis in distinct neurodegenerative diseases. In vitro and in vivo models allow a reliable transition to clinical studies. Several in vitro models, including differentiated SH-SY5Y and PC12 cells, among others, have been used to investigate the pathophysiological mechanisms of distinct neurodegenerative diseases, including ferroptosis. In addition, they can be useful in the development of potential ferroptosis inhibitors that can be used as disease-modifying drugs for the treatment of such diseases. On the other hand, in vivo models based on the manipulation of rodents and invertebrate animals, such as <i>Drosophila melanogaster</i>, <i>Caenorhabditis elegans</i>, and zebrafish, have been increasingly used for research in neurodegeneration. This work provides an up-to-date review of the main in vitro and in vivo models that can be used to evaluate ferroptosis in the most prevalent neurodegenerative diseases, and to explore potential new drug targets and novel drug candidates for effective disease-modifying therapies. |
| first_indexed | 2024-03-11T03:24:12Z |
| format | Article |
| id | doaj.art-3b7f4389adf149f3a5c05fcbbeafe0bc |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:12Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-3b7f4389adf149f3a5c05fcbbeafe0bc2023-11-18T02:50:37ZengMDPI AGPharmaceutics1999-49232023-04-01155136910.3390/pharmaceutics15051369Research Models to Study Ferroptosis’s Impact in Neurodegenerative DiseasesInês Costa0Daniel José Barbosa1Vera Silva2Sofia Benfeito3Fernanda Borges4Fernando Remião5Renata Silva6Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalTOXRUN—Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, PortugalAssociate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalCIQUP-IMS—Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, PortugalCIQUP-IMS—Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, PortugalAssociate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalAssociate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalFerroptosis is a type of regulated cell death promoted by the appearance of oxidative perturbations in the intracellular microenvironment constitutively controlled by glutathione peroxidase 4 (GPX4). It is characterized by increased production of reactive oxygen species, intracellular iron accumulation, lipid peroxidation, inhibition of system Xc-, glutathione depletion, and decreased GPX4 activity. Several pieces of evidence support the involvement of ferroptosis in distinct neurodegenerative diseases. In vitro and in vivo models allow a reliable transition to clinical studies. Several in vitro models, including differentiated SH-SY5Y and PC12 cells, among others, have been used to investigate the pathophysiological mechanisms of distinct neurodegenerative diseases, including ferroptosis. In addition, they can be useful in the development of potential ferroptosis inhibitors that can be used as disease-modifying drugs for the treatment of such diseases. On the other hand, in vivo models based on the manipulation of rodents and invertebrate animals, such as <i>Drosophila melanogaster</i>, <i>Caenorhabditis elegans</i>, and zebrafish, have been increasingly used for research in neurodegeneration. This work provides an up-to-date review of the main in vitro and in vivo models that can be used to evaluate ferroptosis in the most prevalent neurodegenerative diseases, and to explore potential new drug targets and novel drug candidates for effective disease-modifying therapies.https://www.mdpi.com/1999-4923/15/5/1369ferroptosisin vitro modelsin vivo modelsneurodegenerative diseasesneurodegeneration |
| spellingShingle | Inês Costa Daniel José Barbosa Vera Silva Sofia Benfeito Fernanda Borges Fernando Remião Renata Silva Research Models to Study Ferroptosis’s Impact in Neurodegenerative Diseases Pharmaceutics ferroptosis in vitro models in vivo models neurodegenerative diseases neurodegeneration |
| title | Research Models to Study Ferroptosis’s Impact in Neurodegenerative Diseases |
| title_full | Research Models to Study Ferroptosis’s Impact in Neurodegenerative Diseases |
| title_fullStr | Research Models to Study Ferroptosis’s Impact in Neurodegenerative Diseases |
| title_full_unstemmed | Research Models to Study Ferroptosis’s Impact in Neurodegenerative Diseases |
| title_short | Research Models to Study Ferroptosis’s Impact in Neurodegenerative Diseases |
| title_sort | research models to study ferroptosis s impact in neurodegenerative diseases |
| topic | ferroptosis in vitro models in vivo models neurodegenerative diseases neurodegeneration |
| url | https://www.mdpi.com/1999-4923/15/5/1369 |
| work_keys_str_mv | AT inescosta researchmodelstostudyferroptosissimpactinneurodegenerativediseases AT danieljosebarbosa researchmodelstostudyferroptosissimpactinneurodegenerativediseases AT verasilva researchmodelstostudyferroptosissimpactinneurodegenerativediseases AT sofiabenfeito researchmodelstostudyferroptosissimpactinneurodegenerativediseases AT fernandaborges researchmodelstostudyferroptosissimpactinneurodegenerativediseases AT fernandoremiao researchmodelstostudyferroptosissimpactinneurodegenerativediseases AT renatasilva researchmodelstostudyferroptosissimpactinneurodegenerativediseases |