Repurposing of Tibolone in Alzheimer’s Disease

Alzheimer’s disease (AD) is a debilitating neurodegenerative disease characterised by the accumulation of amyloid-beta and tau in the brain, leading to the progressive loss of memory and cognition. The causes of its pathogenesis are still not fully understood, but some risk factors, such as age, gen...

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Main Author: George E. Barreto
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/13/7/1115
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author George E. Barreto
author_facet George E. Barreto
author_sort George E. Barreto
collection DOAJ
description Alzheimer’s disease (AD) is a debilitating neurodegenerative disease characterised by the accumulation of amyloid-beta and tau in the brain, leading to the progressive loss of memory and cognition. The causes of its pathogenesis are still not fully understood, but some risk factors, such as age, genetics, and hormones, may play a crucial role. Studies show that postmenopausal women have a higher risk of developing AD, possibly due to the decrease in hormone levels, especially oestrogen, which may be directly related to a reduction in the activity of oestrogen receptors, especially beta (ERβ), which favours a more hostile cellular environment, leading to mitochondrial dysfunction, mainly affecting key processes related to transport, metabolism, and oxidative phosphorylation. Given the influence of hormones on biological processes at the mitochondrial level, hormone therapies are of clinical interest to reduce the risk or delay the onset of symptoms associated with AD. One drug with such potential is tibolone, which is used in clinics to treat menopause-related symptoms. It can reduce amyloid burden and have benefits on mitochondrial integrity and dynamics. Many of its protective effects are mediated through steroid receptors and may also be related to neuroglobin, whose elevated levels have been shown to protect against neurological diseases. Its importance has increased exponentially due to its implication in the pathogenesis of AD. In this review, we discuss recent advances in tibolone, focusing on its mitochondrial-protective effects, and highlight how valuable this compound could be as a therapeutic alternative to mitigate the molecular pathways characteristic of AD.
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spelling doaj.art-9d7d1a7ebb3d41bfa3a890e30b07f60a2023-11-18T18:31:38ZengMDPI AGBiomolecules2218-273X2023-07-01137111510.3390/biom13071115Repurposing of Tibolone in Alzheimer’s DiseaseGeorge E. Barreto0Department of Biological Sciences, University of Limerick, V94 T9PX Limerick, IrelandAlzheimer’s disease (AD) is a debilitating neurodegenerative disease characterised by the accumulation of amyloid-beta and tau in the brain, leading to the progressive loss of memory and cognition. The causes of its pathogenesis are still not fully understood, but some risk factors, such as age, genetics, and hormones, may play a crucial role. Studies show that postmenopausal women have a higher risk of developing AD, possibly due to the decrease in hormone levels, especially oestrogen, which may be directly related to a reduction in the activity of oestrogen receptors, especially beta (ERβ), which favours a more hostile cellular environment, leading to mitochondrial dysfunction, mainly affecting key processes related to transport, metabolism, and oxidative phosphorylation. Given the influence of hormones on biological processes at the mitochondrial level, hormone therapies are of clinical interest to reduce the risk or delay the onset of symptoms associated with AD. One drug with such potential is tibolone, which is used in clinics to treat menopause-related symptoms. It can reduce amyloid burden and have benefits on mitochondrial integrity and dynamics. Many of its protective effects are mediated through steroid receptors and may also be related to neuroglobin, whose elevated levels have been shown to protect against neurological diseases. Its importance has increased exponentially due to its implication in the pathogenesis of AD. In this review, we discuss recent advances in tibolone, focusing on its mitochondrial-protective effects, and highlight how valuable this compound could be as a therapeutic alternative to mitigate the molecular pathways characteristic of AD.https://www.mdpi.com/2218-273X/13/7/1115Alzheimer’s diseasetibolonemitochondrianeuroglobinoestrogen receptors
spellingShingle George E. Barreto
Repurposing of Tibolone in Alzheimer’s Disease
Biomolecules
Alzheimer’s disease
tibolone
mitochondria
neuroglobin
oestrogen receptors
title Repurposing of Tibolone in Alzheimer’s Disease
title_full Repurposing of Tibolone in Alzheimer’s Disease
title_fullStr Repurposing of Tibolone in Alzheimer’s Disease
title_full_unstemmed Repurposing of Tibolone in Alzheimer’s Disease
title_short Repurposing of Tibolone in Alzheimer’s Disease
title_sort repurposing of tibolone in alzheimer s disease
topic Alzheimer’s disease
tibolone
mitochondria
neuroglobin
oestrogen receptors
url https://www.mdpi.com/2218-273X/13/7/1115
work_keys_str_mv AT georgeebarreto repurposingoftiboloneinalzheimersdisease