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用于治疗阿尔茨海默病的电磁场刺激疗法。

Electromagnetic Field Stimulation Therapy for Alzheimer's Disease.

作者信息

Perez Felipe P, Morisaki Jorge, Kanakri Haitham, Rizkalla Maher

机构信息

Department of Medicine, Indiana University School of Medicine, USA.

Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA.

出版信息

Neurology (Chic). 2024;3(1). Epub 2024 Jan 5.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative dementia worldwide. AD is a multifactorial disease that causes a progressive decline in memory and function precipitated by toxic beta-amyloid (Aβ) proteins, a key player in AD pathology. In 2022, 6.5 million Americans lived with AD, costing the nation $321billion. The standard of care for AD treatment includes acetylcholinesterase inhibitors (AchEIs), NMDA receptor antagonists, and monoclonal antibodies (mAbs). However, these methods are either: 1) ineffective in improving cognition, 2) unable to change disease progression, 3) limited in the number of therapeutic targets, 4) prone to cause severe side effects (brain swelling, microhemorrhages with mAb, and bradycardia and syncope with AchEIs), 5) unable to effectively cross the blood-brain barrier, and 6) lack of understanding of the aging process on the disease. mAbs are available to lower Aβ, but the difficulties of reducing the levels of the toxic Aβ proteins in the brain without triggering brain swelling or microhemorrhages associated with mAbs make the risk-benefit profile of mAbs unclear. A novel multitarget, effective, and safe non-invasive approach utilizing Repeated Electromagnetic Field Stimulation (REMFS) lowers Aβ levels in human neurons and memory areas, prevents neuronal death, stops disease progression, and improves memory without causing brain edema or bleeds in AD mice. This REMFS treatment has not been developed for humans because current EMF devices have poor penetration depth and inhomogeneous E-field distribution in the brain. Here, we discussed the biology of these effects in neurons and the design of optimal devices to treat AD.

摘要

阿尔茨海默病(AD)是全球最常见的神经退行性痴呆。AD是一种多因素疾病,由有毒的β-淀粉样蛋白(Aβ)引发记忆和功能的渐进性衰退,Aβ是AD病理过程中的关键因素。2022年,650万美国人患有AD,给美国造成了3210亿美元的损失。AD治疗的标准方法包括乙酰胆碱酯酶抑制剂(AchEIs)、N-甲基-D-天冬氨酸受体拮抗剂和单克隆抗体(mAbs)。然而,这些方法存在以下问题:1)在改善认知方面无效;2)无法改变疾病进程;3)治疗靶点数量有限;4)容易引发严重副作用(mAb会导致脑肿胀、微出血,AchEIs会导致心动过缓和晕厥);5)无法有效穿过血脑屏障;6)对衰老过程在疾病中的作用缺乏了解。虽然有mAbs可用于降低Aβ水平,但在不引发与mAbs相关的脑肿胀或微出血的情况下降低大脑中有毒Aβ蛋白水平存在困难,使得mAbs的风险效益情况尚不明确。一种利用重复电磁场刺激(REMFS)的新型多靶点、有效且安全的非侵入性方法可降低人类神经元和记忆区域中的Aβ水平,防止神经元死亡,阻止疾病进展,并改善记忆,且不会在AD小鼠中引起脑水肿或出血。由于目前的电磁场设备在大脑中的穿透深度较差且电场分布不均匀,这种REMFS治疗方法尚未用于人类。在此,我们讨论了这些效应在神经元中的生物学机制以及治疗AD的最佳设备设计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ad0/11064876/3ea6cc59f03a/nihms-1961483-f0001.jpg

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