Department of Biological Sciences, University of Limerick, V94 T9PX Limerick, Ireland.
Biomolecules. 2023 Jul 13;13(7):1115. doi: 10.3390/biom13071115.
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.
阿尔茨海默病（AD）是一种使人虚弱的神经退行性疾病，其特征是大脑中淀粉样蛋白-β和 tau 的积累，导致记忆和认知能力的逐渐丧失。其发病机制的原因仍不完全清楚，但一些风险因素，如年龄、遗传和激素，可能起着至关重要的作用。研究表明，绝经后妇女患 AD 的风险较高，可能是由于激素水平下降，特别是雌激素，这可能与雌激素受体（ER），特别是 β 型（ERβ）的活性降低直接相关，这有利于更具敌意的细胞环境，导致线粒体功能障碍，主要影响与运输、代谢和氧化磷酸化相关的关键过程。鉴于激素对线粒体水平生物过程的影响，激素疗法具有临床意义，可以降低与 AD 相关的风险或延缓症状的发生。具有这种潜力的一种药物是替勃龙，它在临床上用于治疗与绝经相关的症状。它可以减少淀粉样蛋白负担，并对线粒体的完整性和动态有好处。其许多保护作用是通过甾体受体介导的，也可能与神经球蛋白有关，神经球蛋白水平升高已被证明可以预防神经疾病。由于其在 AD 发病机制中的作用，它的重要性呈指数级增长。在这篇综述中，我们讨论了替勃龙的最新进展，重点是其对线粒体的保护作用，并强调了这种化合物作为治疗 AD 特征性分子途径的替代疗法的价值。
