Diabetes Drug Discovery: hIAPP1–37 Polymorphic Amyloid Structures as Novel Therapeutic Targets
Human islet amyloid peptide (hIAPP1–37) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAP...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-03-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/3/686 |
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| author | Isaac Fernández-Gómez Marquiza Sablón-Carrazana Alberto Bencomo-Martínez Guadalupe Domínguez Reyna Lara-Martínez Nelly F. Altamirano-Bustamante Luis Felipe Jiménez-García Karina Pasten-Hidalgo Rosa Angélica Castillo-Rodríguez Perla Altamirano Suchitil Rivera Marrero Cristina Revilla-Monsalve Peter Valdés-Sosa Fabio Salamanca-Gómez Eulalia Garrido-Magaña Chryslaine Rodríguez-Tanty Myriam M. Altamirano-Bustamante |
| author_facet | Isaac Fernández-Gómez Marquiza Sablón-Carrazana Alberto Bencomo-Martínez Guadalupe Domínguez Reyna Lara-Martínez Nelly F. Altamirano-Bustamante Luis Felipe Jiménez-García Karina Pasten-Hidalgo Rosa Angélica Castillo-Rodríguez Perla Altamirano Suchitil Rivera Marrero Cristina Revilla-Monsalve Peter Valdés-Sosa Fabio Salamanca-Gómez Eulalia Garrido-Magaña Chryslaine Rodríguez-Tanty Myriam M. Altamirano-Bustamante |
| author_sort | Isaac Fernández-Gómez |
| collection | DOAJ |
| description | Human islet amyloid peptide (hIAPP1–37) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP1–37) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP1–37 aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP1–37. When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP1–37. Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP1–37 oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A–F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities. |
| first_indexed | 2024-12-21T16:21:36Z |
| format | Article |
| id | doaj.art-b8c1b1834cc6469c89a87b331ebe453f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T16:21:36Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b8c1b1834cc6469c89a87b331ebe453f2022-12-21T18:57:33ZengMDPI AGMolecules1420-30492018-03-0123368610.3390/molecules23030686molecules23030686Diabetes Drug Discovery: hIAPP1–37 Polymorphic Amyloid Structures as Novel Therapeutic TargetsIsaac Fernández-Gómez0Marquiza Sablón-Carrazana1Alberto Bencomo-Martínez2Guadalupe Domínguez3Reyna Lara-Martínez4Nelly F. Altamirano-Bustamante5Luis Felipe Jiménez-García6Karina Pasten-Hidalgo7Rosa Angélica Castillo-Rodríguez8Perla Altamirano9Suchitil Rivera Marrero10Cristina Revilla-Monsalve11Peter Valdés-Sosa12Fabio Salamanca-Gómez13Eulalia Garrido-Magaña14Chryslaine Rodríguez-Tanty15Myriam M. Altamirano-Bustamante16Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México 06720, MexicoDepartamento de Neuroquímica, Centro de Neurociencias de Cuba, Habana 11600, CubaDepartamento de Neuroquímica, Centro de Neurociencias de Cuba, Habana 11600, CubaInstituto de Fisiología Celular, UNAM, Ciudad de México 04510, MexicoDepartamento de Biología Celular, Facultad de Ciencias, UNAM, Ciudad de México 04510, MexicoInstituto Nacional de Pediatría, Ciudad de México 04530, MexicoDepartamento de Biología Celular, Facultad de Ciencias, UNAM, Ciudad de México 04510, MexicoInstituto Nacional de Pediatría, Ciudad de México 04530, MexicoInstituto Nacional de Pediatría, Ciudad de México 04530, MexicoServicio de Medicina Nuclear, Hospital de Especialidades, CMN, La Raza, Instituto Mexicano del Seguro Social, Ciudad de México 06720, MexicoDepartamento de Neuroquímica, Centro de Neurociencias de Cuba, Habana 11600, CubaUnidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México 06720, MexicoDepartamento de Neuroquímica, Centro de Neurociencias de Cuba, Habana 11600, CubaCoordinación de Investigación en Salud, Instituto Mexicano del Seguro Social, Ciudad de México 06720, MexicoUMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México 06720, MexicoDepartamento de Neuroquímica, Centro de Neurociencias de Cuba, Habana 11600, CubaUnidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México 06720, MexicoHuman islet amyloid peptide (hIAPP1–37) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP1–37) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP1–37 aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP1–37. When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP1–37. Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP1–37 oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A–F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities.http://www.mdpi.com/1420-3049/23/3/686IAPPdiabetes mellituspharmacological chaperonesamyloid structuresconformational diseasesdrug discovery |
| spellingShingle | Isaac Fernández-Gómez Marquiza Sablón-Carrazana Alberto Bencomo-Martínez Guadalupe Domínguez Reyna Lara-Martínez Nelly F. Altamirano-Bustamante Luis Felipe Jiménez-García Karina Pasten-Hidalgo Rosa Angélica Castillo-Rodríguez Perla Altamirano Suchitil Rivera Marrero Cristina Revilla-Monsalve Peter Valdés-Sosa Fabio Salamanca-Gómez Eulalia Garrido-Magaña Chryslaine Rodríguez-Tanty Myriam M. Altamirano-Bustamante Diabetes Drug Discovery: hIAPP1–37 Polymorphic Amyloid Structures as Novel Therapeutic Targets Molecules IAPP diabetes mellitus pharmacological chaperones amyloid structures conformational diseases drug discovery |
| title | Diabetes Drug Discovery: hIAPP1–37 Polymorphic Amyloid Structures as Novel Therapeutic Targets |
| title_full | Diabetes Drug Discovery: hIAPP1–37 Polymorphic Amyloid Structures as Novel Therapeutic Targets |
| title_fullStr | Diabetes Drug Discovery: hIAPP1–37 Polymorphic Amyloid Structures as Novel Therapeutic Targets |
| title_full_unstemmed | Diabetes Drug Discovery: hIAPP1–37 Polymorphic Amyloid Structures as Novel Therapeutic Targets |
| title_short | Diabetes Drug Discovery: hIAPP1–37 Polymorphic Amyloid Structures as Novel Therapeutic Targets |
| title_sort | diabetes drug discovery hiapp1 37 polymorphic amyloid structures as novel therapeutic targets |
| topic | IAPP diabetes mellitus pharmacological chaperones amyloid structures conformational diseases drug discovery |
| url | http://www.mdpi.com/1420-3049/23/3/686 |
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