Insulin growth factor binding protein 7 is a novel target to treat dementia
Alzheimer's disease (AD) is the most common form of dementia in the elderly but effective therapeutic strategies to treat AD are not yet available. This is also due to the fact that the pathological mechanisms that drive the pathogenesis of sporadic AD are still not sufficiently understood and...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-02-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999611300257X |
| _version_ | 1818610539788500992 |
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| author | Hope Y. Agbemenyah Roberto C. Agis-Balboa Susanne Burkhardt Ivana Delalle Andre Fischer |
| author_facet | Hope Y. Agbemenyah Roberto C. Agis-Balboa Susanne Burkhardt Ivana Delalle Andre Fischer |
| author_sort | Hope Y. Agbemenyah |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is the most common form of dementia in the elderly but effective therapeutic strategies to treat AD are not yet available. This is also due to the fact that the pathological mechanisms that drive the pathogenesis of sporadic AD are still not sufficiently understood and may differ on the individual level. Several risk factors such as altered insulin-like peptide (ILP) signaling have been linked to AD and modulating the ILP system has been discussed as a potential therapeutic avenue. Here we show that insulin-like growth factor binding protein 7 (IGFBP7), a protein that attenuates the function of ILPs, is up-regulated in the brains of AD patients and in a mouse model for AD via a process that involves altered DNA-methylation and coincides with decreased ILP signaling. Mimicking the AD-situation in wild type mice, by increasing hippocampal IGFBP7 levels leads to impaired memory consolidation. Consistently, inhibiting IGFBP7 function in mice that develop AD-like memory impairment reinstates associative learning behavior. These data suggest that IGFBP7 is a critical regulator of memory consolidation and might be used as a biomarker for AD. Targeting IGFBP7 could be a novel therapeutic avenue for the treatment of AD patients. |
| first_indexed | 2024-12-16T15:16:03Z |
| format | Article |
| id | doaj.art-6d158999330448e090297a8e92ad4b66 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T15:16:03Z |
| publishDate | 2014-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-6d158999330448e090297a8e92ad4b662022-12-21T22:26:47ZengElsevierNeurobiology of Disease1095-953X2014-02-0162135143Insulin growth factor binding protein 7 is a novel target to treat dementiaHope Y. Agbemenyah0Roberto C. Agis-Balboa1Susanne Burkhardt2Ivana Delalle3Andre Fischer4Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Grisebachstr. 5, 37077 Göttingen, GermanyDepartment of Psychiatry and Psychotherapy, University Medical Center Göttingen, Grisebachstr. 5, 37077 Göttingen, GermanyGerman Center for Neurodegenerative Diseases (DZNE) Göttingen, Grisebachstr. 5, 37077 Göttingen, GermanyDepartment of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USADepartment of Psychiatry and Psychotherapy, University Medical Center Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE) Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany; Corresponding author at: Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, University Goettingen, German Center for Neurodegenerative Diseases (DZNE) Goettingen, Grisebachstr. 5, D-37077 Goettingen, Germany.Alzheimer's disease (AD) is the most common form of dementia in the elderly but effective therapeutic strategies to treat AD are not yet available. This is also due to the fact that the pathological mechanisms that drive the pathogenesis of sporadic AD are still not sufficiently understood and may differ on the individual level. Several risk factors such as altered insulin-like peptide (ILP) signaling have been linked to AD and modulating the ILP system has been discussed as a potential therapeutic avenue. Here we show that insulin-like growth factor binding protein 7 (IGFBP7), a protein that attenuates the function of ILPs, is up-regulated in the brains of AD patients and in a mouse model for AD via a process that involves altered DNA-methylation and coincides with decreased ILP signaling. Mimicking the AD-situation in wild type mice, by increasing hippocampal IGFBP7 levels leads to impaired memory consolidation. Consistently, inhibiting IGFBP7 function in mice that develop AD-like memory impairment reinstates associative learning behavior. These data suggest that IGFBP7 is a critical regulator of memory consolidation and might be used as a biomarker for AD. Targeting IGFBP7 could be a novel therapeutic avenue for the treatment of AD patients.http://www.sciencedirect.com/science/article/pii/S096999611300257XInsulin-like growth factor binding proteinsAlzheimerEpigeneticsLearning and memory |
| spellingShingle | Hope Y. Agbemenyah Roberto C. Agis-Balboa Susanne Burkhardt Ivana Delalle Andre Fischer Insulin growth factor binding protein 7 is a novel target to treat dementia Neurobiology of Disease Insulin-like growth factor binding proteins Alzheimer Epigenetics Learning and memory |
| title | Insulin growth factor binding protein 7 is a novel target to treat dementia |
| title_full | Insulin growth factor binding protein 7 is a novel target to treat dementia |
| title_fullStr | Insulin growth factor binding protein 7 is a novel target to treat dementia |
| title_full_unstemmed | Insulin growth factor binding protein 7 is a novel target to treat dementia |
| title_short | Insulin growth factor binding protein 7 is a novel target to treat dementia |
| title_sort | insulin growth factor binding protein 7 is a novel target to treat dementia |
| topic | Insulin-like growth factor binding proteins Alzheimer Epigenetics Learning and memory |
| url | http://www.sciencedirect.com/science/article/pii/S096999611300257X |
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