中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (1): 54-66.doi: 10.4103/NRR.NRR-D-23-01827

• 综述:退行性病与再生 • 上一篇    下一篇

淀粉样蛋白-β介导的阿尔茨海默病病理生理学靶向表观遗传学机制:揭示治疗潜力

  

  • 出版日期:2025-01-15 发布日期:2025-01-15

Targeting epigenetic mechanisms in amyloid-β–mediated Alzheimer’s pathophysiology: unveiling therapeutic potential

Jennie Z. Li, Nagendran Ramalingam, Shaomin Li*   

  1. Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
  • Online:2025-01-15 Published:2025-01-15
  • Contact: Shaomin Li, MD, PhD, sli11@bwh.harvard.edu.
  • Supported by:
    This work was supported by a grant from the Massachusetts Alzheimer’s Disease Research Center (5P50 AG 005134) (to SL).

摘要: https://orcid.org/0000-0001-9451-2151 (Shaomin Li)

Abstract: Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia. Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-β oligomers in the brain, influenced by complex genetic and environmental factors. The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction. Throughout life, environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders. These changes, known as epigenetic modifications, also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity. In this context, we highlight recent advances in understanding the roles played by key components of the epigenetic machinery, specifically DNA methylation, histone modification, and microRNAs, in the development of Alzheimer’s disease, synaptic function, and activity-dependent synaptic plasticity. Moreover, we explore various strategies, including enriched environments, exposure to non-invasive brain stimulation, and the use of pharmacological agents, aimed at improving synaptic function and enhancing long-term potentiation, a process integral to epigenetic mechanisms. Lastly, we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease. We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

Key words: Alzheimer’s disease, DNA methylation, enriched environments, histone modification, microRNAs, non-invasive brain stimulation, synaptic plasticity