Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's disease
The increasing prevalence of Alzheimer's disease (AD) calls for a comprehensive exploration of its complex etiology, with a focus on sex-specific vulnerability, particularly the heightened susceptibility observed in postmenopausal women. Neurometabolic alterations during the endocrine transitio...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Experimental Gerontology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556525000075 |
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| author | Christopher O'Mahony Oscar Hidalgo-Lanussa George E. Barreto |
| author_facet | Christopher O'Mahony Oscar Hidalgo-Lanussa George E. Barreto |
| author_sort | Christopher O'Mahony |
| collection | DOAJ |
| description | The increasing prevalence of Alzheimer's disease (AD) calls for a comprehensive exploration of its complex etiology, with a focus on sex-specific vulnerability, particularly the heightened susceptibility observed in postmenopausal women. Neurometabolic alterations during the endocrine transition emerge as early indicators of AD pathology, including reduced glucose metabolism and increased amyloid-beta (Aβ) deposition. The fluctuating endocrine environment, marked by declining estradiol levels and reduced estrogen receptor beta (ERβ) activity, further exacerbates this process. In this context, here we explore the potential of forkhead box O3 (FOXO3) as a critical mediator linking metabolic disturbances to hormonal decline. We propose that FOXO3 plays a key role in the intersection of menopause and AD, given its dysregulation in both AD patients and postmenopausal women, modulating cellular metabolism through interactions with the AMPK/AKT/PI3K pathways. This relationship highlights the intersection between hormonal changes and increased AD susceptibility. This review aims to open a discussion on FOXO3's contribution to the metabolic dysregulation seen in menopause and its impact on the progression of AD. Understanding the functional role of FOXO3 in menopause-associated metabolic changes could lead to targeted therapeutic strategies, offering novel insights for managing for this condition. |
| format | Article |
| id | doaj-art-dede5824c82c4514a793f30d6634bd5c |
| institution | Kabale University |
| issn | 1873-6815 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental Gerontology |
| spelling | doaj-art-dede5824c82c4514a793f30d6634bd5c2025-01-31T05:10:08ZengElsevierExperimental Gerontology1873-68152025-02-01200112679Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's diseaseChristopher O'Mahony0Oscar Hidalgo-Lanussa1George E. Barreto2Department of Biological Sciences, University of Limerick, Limerick V94 T9PX, IrelandDepartment of Biological Sciences, University of Limerick, Limerick V94 T9PX, IrelandCorresponding author.; Department of Biological Sciences, University of Limerick, Limerick V94 T9PX, IrelandThe increasing prevalence of Alzheimer's disease (AD) calls for a comprehensive exploration of its complex etiology, with a focus on sex-specific vulnerability, particularly the heightened susceptibility observed in postmenopausal women. Neurometabolic alterations during the endocrine transition emerge as early indicators of AD pathology, including reduced glucose metabolism and increased amyloid-beta (Aβ) deposition. The fluctuating endocrine environment, marked by declining estradiol levels and reduced estrogen receptor beta (ERβ) activity, further exacerbates this process. In this context, here we explore the potential of forkhead box O3 (FOXO3) as a critical mediator linking metabolic disturbances to hormonal decline. We propose that FOXO3 plays a key role in the intersection of menopause and AD, given its dysregulation in both AD patients and postmenopausal women, modulating cellular metabolism through interactions with the AMPK/AKT/PI3K pathways. This relationship highlights the intersection between hormonal changes and increased AD susceptibility. This review aims to open a discussion on FOXO3's contribution to the metabolic dysregulation seen in menopause and its impact on the progression of AD. Understanding the functional role of FOXO3 in menopause-associated metabolic changes could lead to targeted therapeutic strategies, offering novel insights for managing for this condition.http://www.sciencedirect.com/science/article/pii/S0531556525000075Alzheimer's diseaseMenopauseGonadal hormonesSteroid hormonesMitochondriaFOXO3 |
| spellingShingle | Christopher O'Mahony Oscar Hidalgo-Lanussa George E. Barreto Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's disease Experimental Gerontology Alzheimer's disease Menopause Gonadal hormones Steroid hormones Mitochondria FOXO3 |
| title | Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's disease |
| title_full | Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's disease |
| title_fullStr | Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's disease |
| title_full_unstemmed | Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's disease |
| title_short | Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's disease |
| title_sort | unveiling foxo3 s metabolic contribution to menopause and alzheimer s disease |
| topic | Alzheimer's disease Menopause Gonadal hormones Steroid hormones Mitochondria FOXO3 |
| url | http://www.sciencedirect.com/science/article/pii/S0531556525000075 |
| work_keys_str_mv | AT christopheromahony unveilingfoxo3smetaboliccontributiontomenopauseandalzheimersdisease AT oscarhidalgolanussa unveilingfoxo3smetaboliccontributiontomenopauseandalzheimersdisease AT georgeebarreto unveilingfoxo3smetaboliccontributiontomenopauseandalzheimersdisease |