LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress
ABSTRACT: Parkinson’s disease (PD) is a complex multifactorial progressive neurodegenerative disease characterized by locomotor alteration due to the specific deterioration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc). Mounting evidence shows that human LRRK2 (hLRRK...
- Autores:
-
Quintero Espinosa, Diana Alejandra
Jiménez del Río, Marlene
Vélez Pardo, Carlos Alberto
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2024
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/39784
- Acceso en línea:
- https://hdl.handle.net/10495/39784
- Palabra clave:
- Drosophila
Paraquat
Estrés Oxidativo
Oxidative Stress
Inhibidores de Proteínas Quinasas
Protein Kinase Inhibitors
Enfermedad de Parkinson
Parkinson Disease
https://id.nlm.nih.gov/mesh/D004330
https://id.nlm.nih.gov/mesh/D010269
https://id.nlm.nih.gov/mesh/D018384
https://id.nlm.nih.gov/mesh/D047428
https://id.nlm.nih.gov/mesh/D010300
- Rights
- openAccess
- License
- http://creativecommons.org/licenses/by/2.5/co/
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LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress |
| title |
LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress |
| spellingShingle |
LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress Drosophila Paraquat Estrés Oxidativo Oxidative Stress Inhibidores de Proteínas Quinasas Protein Kinase Inhibitors Enfermedad de Parkinson Parkinson Disease https://id.nlm.nih.gov/mesh/D004330 https://id.nlm.nih.gov/mesh/D010269 https://id.nlm.nih.gov/mesh/D018384 https://id.nlm.nih.gov/mesh/D047428 https://id.nlm.nih.gov/mesh/D010300 |
| title_short |
LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress |
| title_full |
LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress |
| title_fullStr |
LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress |
| title_full_unstemmed |
LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress |
| title_sort |
LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress |
| dc.creator.fl_str_mv |
Quintero Espinosa, Diana Alejandra Jiménez del Río, Marlene Vélez Pardo, Carlos Alberto |
| dc.contributor.author.none.fl_str_mv |
Quintero Espinosa, Diana Alejandra Jiménez del Río, Marlene Vélez Pardo, Carlos Alberto |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de Neurociencias de Antioquia |
| dc.subject.decs.none.fl_str_mv |
Drosophila Paraquat Estrés Oxidativo Oxidative Stress Inhibidores de Proteínas Quinasas Protein Kinase Inhibitors Enfermedad de Parkinson Parkinson Disease |
| topic |
Drosophila Paraquat Estrés Oxidativo Oxidative Stress Inhibidores de Proteínas Quinasas Protein Kinase Inhibitors Enfermedad de Parkinson Parkinson Disease https://id.nlm.nih.gov/mesh/D004330 https://id.nlm.nih.gov/mesh/D010269 https://id.nlm.nih.gov/mesh/D018384 https://id.nlm.nih.gov/mesh/D047428 https://id.nlm.nih.gov/mesh/D010300 |
| dc.subject.meshuri.none.fl_str_mv |
https://id.nlm.nih.gov/mesh/D004330 https://id.nlm.nih.gov/mesh/D010269 https://id.nlm.nih.gov/mesh/D018384 https://id.nlm.nih.gov/mesh/D047428 https://id.nlm.nih.gov/mesh/D010300 |
| description |
ABSTRACT: Parkinson’s disease (PD) is a complex multifactorial progressive neurodegenerative disease characterized by locomotor alteration due to the specific deterioration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc). Mounting evidence shows that human LRRK2 (hLRRK2) kinase activity is involved in oxidative stress (OS)-induced neurodegeneration, suggesting LRRK2 inhibition as a potential therapeutic target. We report that the hLRRK2 inhibitor PF-06447475 (PF-475) prolonged lifespan, increased locomotor activity, maintained DAergic neuronal integrity, and reduced lipid peroxidation (LPO) in female Drosophila melanogaster flies chronically exposed to paraquat (PQ), a redox cycling compound, compared to flies treated with vehicle only. Since LRRK2 is an evolutionary conserved kinase, the present findings reinforce the idea that either reduction or inhibition of the LRRK2 kinase might decrease OS and locomotor alterations associated with PD. Our observations highlight the importance of uncovering the function of the hLRRK2 orthologue dLrrk2 in D. melanogaster as an excellent model for pharmacological screenings. |
| publishDate |
2024 |
| dc.date.accessioned.none.fl_str_mv |
2024-06-08T12:29:22Z |
| dc.date.available.none.fl_str_mv |
2024-06-08T12:29:22Z |
| dc.date.issued.none.fl_str_mv |
2024 |
| dc.type.spa.fl_str_mv |
Artículo de investigación |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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https://purl.org/redcol/resource_type/ART |
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http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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Quintero-Espinosa DA, Jimenez-Del-Rio M, Velez-Pardo C. LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress. Neurochem Res. 2024 Jun 7. doi: 10.1007/s11064-024-04141-9. |
| dc.identifier.issn.none.fl_str_mv |
0364-3190 |
| dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/10495/39784 |
| dc.identifier.doi.none.fl_str_mv |
10.1007/s11064-024-04141-9 |
| dc.identifier.eissn.none.fl_str_mv |
1573-6903 |
| identifier_str_mv |
Quintero-Espinosa DA, Jimenez-Del-Rio M, Velez-Pardo C. LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress. Neurochem Res. 2024 Jun 7. doi: 10.1007/s11064-024-04141-9. 0364-3190 10.1007/s11064-024-04141-9 1573-6903 |
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https://hdl.handle.net/10495/39784 |
| dc.language.iso.spa.fl_str_mv |
eng |
| language |
eng |
| dc.relation.ispartofjournalabbrev.spa.fl_str_mv |
Neurochem. Res. |
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13 |
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1 |
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Neurochemical Research |
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http://creativecommons.org/licenses/by/2.5/co/ |
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https://creativecommons.org/licenses/by/4.0/ |
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13 páginas |
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Springer |
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Nueva York, Estados Unidos |
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Quintero Espinosa, Diana AlejandraJiménez del Río, MarleneVélez Pardo, Carlos AlbertoGrupo de Neurociencias de Antioquia2024-06-08T12:29:22Z2024-06-08T12:29:22Z2024Quintero-Espinosa DA, Jimenez-Del-Rio M, Velez-Pardo C. LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress. Neurochem Res. 2024 Jun 7. doi: 10.1007/s11064-024-04141-9.0364-3190https://hdl.handle.net/10495/3978410.1007/s11064-024-04141-91573-6903ABSTRACT: Parkinson’s disease (PD) is a complex multifactorial progressive neurodegenerative disease characterized by locomotor alteration due to the specific deterioration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc). Mounting evidence shows that human LRRK2 (hLRRK2) kinase activity is involved in oxidative stress (OS)-induced neurodegeneration, suggesting LRRK2 inhibition as a potential therapeutic target. We report that the hLRRK2 inhibitor PF-06447475 (PF-475) prolonged lifespan, increased locomotor activity, maintained DAergic neuronal integrity, and reduced lipid peroxidation (LPO) in female Drosophila melanogaster flies chronically exposed to paraquat (PQ), a redox cycling compound, compared to flies treated with vehicle only. Since LRRK2 is an evolutionary conserved kinase, the present findings reinforce the idea that either reduction or inhibition of the LRRK2 kinase might decrease OS and locomotor alterations associated with PD. Our observations highlight the importance of uncovering the function of the hLRRK2 orthologue dLrrk2 in D. melanogaster as an excellent model for pharmacological screenings.Universidad de Antioquia. Vicerrectoría de investigación. Comité para el Desarrollo de la Investigación - CODICOL001074413 páginasapplication/pdfengSpringerNueva York, Estados Unidoshttp://creativecommons.org/licenses/by/2.5/co/https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative StressArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionDrosophilaParaquatEstrés OxidativoOxidative StressInhibidores de Proteínas QuinasasProtein Kinase InhibitorsEnfermedad de ParkinsonParkinson Diseasehttps://id.nlm.nih.gov/mesh/D004330https://id.nlm.nih.gov/mesh/D010269https://id.nlm.nih.gov/mesh/D018384https://id.nlm.nih.gov/mesh/D047428https://id.nlm.nih.gov/mesh/D010300Neurochem. 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