整合表观遗传修饰和干细胞治疗策略:推进阿尔茨海默病治疗的新方法-文献综述。

Narra J Pub Date : 2024-12-01 Epub Date: 2024-12-02 DOI:10.52225/narra.v4i3.202
Edhijanto Widaja, Jeanne A Pawitan
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引用次数: 0

摘要

阿尔茨海默病(AD)是最常见的痴呆症形式,是一种日益加重的全球负担,特别是在印度尼西亚等人口开始显著老龄化的国家。目前的药物,包括胆碱酯酶抑制剂和NMDA受体拮抗剂,对早期到中期的临床症状有适度的影响,尽管取得了进展,但迄今为止还没有治愈性的治疗方法。激活或抑制表观遗传修饰,包括DNA甲基化,组蛋白修饰和microRNA调控,似乎在AD的发展中发挥重要作用。这些改变进一步导致了与淀粉样蛋白-β沉积、tau蛋白功能障碍、神经炎症和神经元死亡等AD标志性病理相关的转录改变。由于表观遗传学的可逆性及其纠正错误基因表达的能力,我们讨论了靶向这些表观遗传改变作为一种新的治疗策略的可行性。我们还回顾了干细胞治疗和表观遗传调节在神经退行性疾病、炎症和认知能力下降中的联合前景。这种联合方法可能提供一种多方面的策略,以减缓疾病进展,取代失去的神经元,并恢复神经功能。尽管存在包括伦理、经济和方法障碍在内的挑战,表观遗传调控和干细胞治疗的持续研究仍有望成为阿尔茨海默病的先驱疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrating epigenetic modification and stem cell therapy strategies: A novel approach for advancing Alzheimer's disease treatment - A literature review.

Alzheimer's disease (AD) is the most frequent form of dementia and represents an increasing global burden, particularly in countries like Indonesia, where the population has begun to age significantly. Current medications, including cholinesterase inhibitors and NMDA receptor antagonists, have modest effects on clinical symptoms in the early to middle stages, but there is no curative treatment available so far despite progress. Activating or repressing epigenetic modifications, including DNA methylation, histone modification and microRNA regulation, appears to play an important role in AD development. These alterations further enact transcriptional changes relevant to the signature AD pathologies of amyloid-β deposition, tau protein malfunctioning, neuroinflammation, and neuronal death. Here, we discuss the feasibility of targeting these epigenetic alterations as a new treatment strategy due to the reversibility of epigenetics and their ability to correct faulty gene expression. We also review the combined promise of stem cell therapies and epigenetic modulation in neurodegeneration, inflammation and cognitive decline. This combined approach may provide a multifaceted strategy to slow disease progression, replace lost neurons, and restore neural function. Despite challenges, including ethical, financial, and methodological barriers, ongoing research in epigenetic modulation and stem cell therapy holds promise for pioneering therapies in AD.

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