The role of insulin-like growth factor-I in the physiopathology of hearing
Insulin like growth factor I (IGF-I) belongs to the family of polypeptides of insulin, which play a central role in embryonic development and adult nervous system homeostasis by endocrine, autocrine and paracrine mechanisms. IGF-I is fundamental for the regulation of cochlear development, growth an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2011-07-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnmol.2011.00011/full |
| _version_ | 1818465873426382848 |
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| author | Silvia eMurillo-Cuesta Silvia eMurillo-Cuesta Lourdes eRodríguez-de La Rosa Lourdes eRodríguez-de La Rosa Luis eLassaleta Luis eLassaleta Rafael eCediel Rafael eCediel Rafael eCediel Isabel eVarela-Nieto Isabel eVarela-Nieto Isabel eVarela-Nieto |
| author_facet | Silvia eMurillo-Cuesta Silvia eMurillo-Cuesta Lourdes eRodríguez-de La Rosa Lourdes eRodríguez-de La Rosa Luis eLassaleta Luis eLassaleta Rafael eCediel Rafael eCediel Rafael eCediel Isabel eVarela-Nieto Isabel eVarela-Nieto Isabel eVarela-Nieto |
| author_sort | Silvia eMurillo-Cuesta |
| collection | DOAJ |
| description | Insulin like growth factor I (IGF-I) belongs to the family of polypeptides of insulin, which play a central role in embryonic development and adult nervous system homeostasis by endocrine, autocrine and paracrine mechanisms. IGF-I is fundamental for the regulation of cochlear development, growth and differentiation, and its mutations are associated with hearing loss in mice and men. Low levels of IGF-I have been shown to correlate with different human syndromes showing hearing loss and with presbyacusis. Animal models are fundamental to understand the genetic, epigenetic, and environmental factors that contribute to human hearing loss. In the mouse, IGF-I serum levels decrease with ageing and there is a concomitant hearing loss and retinal degeneration. In the Igf1-/- null mouse, hearing loss is due to neuronal loss, poor innervation of the sensory hair cells and age-related stria vascularis alterations. In the inner ear, IGF-I actions are mediated by intracellular signaling networks, RAF, AKT and p38 MAPK protein kinases modulate the expression and activity of transcription factors, as AP1, MEF2, FoxM1 and FoxP3, leading to the regulation of cell cycle and metabolism. Therapy with rhIGF-I has been approved in humans for the treatment of poor linear growth and certain neurodegenerative diseases. This review will discuss these findings and their implications in new IGF-I-based treatments for the protection or repair of hearing loss. |
| first_indexed | 2024-04-13T20:51:29Z |
| format | Article |
| id | doaj.art-27f4e54bf697418490c561f8b8631b23 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-13T20:51:29Z |
| publishDate | 2011-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-27f4e54bf697418490c561f8b8631b232022-12-22T02:30:30ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992011-07-01410.3389/fnmol.2011.0001112336The role of insulin-like growth factor-I in the physiopathology of hearingSilvia eMurillo-Cuesta0Silvia eMurillo-Cuesta1Lourdes eRodríguez-de La Rosa2Lourdes eRodríguez-de La Rosa3Luis eLassaleta4Luis eLassaleta5Rafael eCediel6Rafael eCediel7Rafael eCediel8Isabel eVarela-Nieto9Isabel eVarela-Nieto10Isabel eVarela-Nieto11Consejo Superior de Investigaciones Científicas-Universidad Autónoma de MadridInstituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas-Universidad Autónoma de MadridInstituto de Salud Carlos IIIHospital La PazInstituto de Investigación Sanitaria IdiPAZInstituto de Salud Carlos IIIUniversidad ComplutenseConsejo Superior de Investigaciones Científicas-Universidad Autónoma de MadridConsejo Superior de Investigaciones Científicas-Universidad Autónoma de MadridInstituto de Salud Carlos IIIInstituto de Investigación Sanitaria IdiPAZInsulin like growth factor I (IGF-I) belongs to the family of polypeptides of insulin, which play a central role in embryonic development and adult nervous system homeostasis by endocrine, autocrine and paracrine mechanisms. IGF-I is fundamental for the regulation of cochlear development, growth and differentiation, and its mutations are associated with hearing loss in mice and men. Low levels of IGF-I have been shown to correlate with different human syndromes showing hearing loss and with presbyacusis. Animal models are fundamental to understand the genetic, epigenetic, and environmental factors that contribute to human hearing loss. In the mouse, IGF-I serum levels decrease with ageing and there is a concomitant hearing loss and retinal degeneration. In the Igf1-/- null mouse, hearing loss is due to neuronal loss, poor innervation of the sensory hair cells and age-related stria vascularis alterations. In the inner ear, IGF-I actions are mediated by intracellular signaling networks, RAF, AKT and p38 MAPK protein kinases modulate the expression and activity of transcription factors, as AP1, MEF2, FoxM1 and FoxP3, leading to the regulation of cell cycle and metabolism. Therapy with rhIGF-I has been approved in humans for the treatment of poor linear growth and certain neurodegenerative diseases. This review will discuss these findings and their implications in new IGF-I-based treatments for the protection or repair of hearing loss.http://journal.frontiersin.org/Journal/10.3389/fnmol.2011.00011/fullDeafnessOrgan of CortiHuman geneticsAnimal ModelsIGF1R signalingInsulin-like factors |
| spellingShingle | Silvia eMurillo-Cuesta Silvia eMurillo-Cuesta Lourdes eRodríguez-de La Rosa Lourdes eRodríguez-de La Rosa Luis eLassaleta Luis eLassaleta Rafael eCediel Rafael eCediel Rafael eCediel Isabel eVarela-Nieto Isabel eVarela-Nieto Isabel eVarela-Nieto The role of insulin-like growth factor-I in the physiopathology of hearing Frontiers in Molecular Neuroscience Deafness Organ of Corti Human genetics Animal Models IGF1R signaling Insulin-like factors |
| title | The role of insulin-like growth factor-I in the physiopathology of hearing |
| title_full | The role of insulin-like growth factor-I in the physiopathology of hearing |
| title_fullStr | The role of insulin-like growth factor-I in the physiopathology of hearing |
| title_full_unstemmed | The role of insulin-like growth factor-I in the physiopathology of hearing |
| title_short | The role of insulin-like growth factor-I in the physiopathology of hearing |
| title_sort | role of insulin like growth factor i in the physiopathology of hearing |
| topic | Deafness Organ of Corti Human genetics Animal Models IGF1R signaling Insulin-like factors |
| url | http://journal.frontiersin.org/Journal/10.3389/fnmol.2011.00011/full |
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