Liu Yanzhi, Aquili Luca, Wong Kah Hui, Lu Zhiliang, Lim Lee Wei
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Department of Biosciences and Bioinformatics, and Suzhou Municipal Key Laboratory of Cancer Biology and Chronic Disease, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China; School of Management, Ritsumeikan Asia Pacific University, Beppu, Oita, Japan.
Ageing Res Rev. 2025 Jun;108:102755. doi: 10.1016/j.arr.2025.102755. Epub 2025 Apr 14.
With population aging, Alzheimer's disease (AD) is becoming increasingly prevalent, causing great health and economic burdens worldwide. Despite decades of research, there are still no effective disease-modifying treatments for AD, highlighting the urgent need for more in-depth understanding of the disease-causing mechanisms. The brain serotonin (5-HT) neurotransmission system undergoes structural and functional changes in aging and AD, which contributes to cognitive decline and comorbid mood disturbances. This review discusses the critical involvement of the brain 5-HT system in aging and AD. Existing findings on the changes in projection fiber innervation and receptor/transporter expression in AD are reviewed. Preclinical and clinical progress on the development of 5-HT-modulating drugs for AD and the obstacles faced by these development efforts are discussed. Epigenetic control of the brain 5-HT system and the potential of modulating 5-HT transmission via DNA methylation are also examined.
随着人口老龄化，阿尔茨海默病（AD）日益普遍，给全球带来了巨大的健康和经济负担。尽管经过了数十年的研究，但仍然没有针对AD的有效疾病修饰治疗方法，这凸显了更深入了解致病机制的迫切需求。大脑血清素（5-HT）神经传递系统在衰老和AD过程中会发生结构和功能变化，这会导致认知能力下降和并发情绪障碍。本综述讨论了大脑5-HT系统在衰老和AD中的关键作用。综述了AD中投射纤维支配和受体/转运体表达变化的现有研究结果。讨论了用于AD的5-HT调节药物开发方面的临床前和临床进展以及这些开发工作面临的障碍。还研究了大脑5-HT系统的表观遗传控制以及通过DNA甲基化调节5-HT传递的潜力。
