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阿尔茨海默病:治疗策略及其局限性。

Alzheimer's Disease: Treatment Strategies and Their Limitations.

机构信息

LIBio Laboratory, University of Lorraine, 54505 Vandoeuvre-lès-Nancy, France.

UR AFPA Laboratory, Qualivie Team, University of Lorraine, 54505 Vandoeuvre-lès-Nancy, France.

出版信息

Int J Mol Sci. 2022 Nov 12;23(22):13954. doi: 10.3390/ijms232213954.

Abstract

Alzheimer's disease (AD) is the most frequent case of neurodegenerative disease and is becoming a major public health problem all over the world. Many therapeutic strategies have been explored for several decades; however, there is still no curative treatment, and the priority remains prevention. In this review, we present an update on the clinical and physiological phase of the AD spectrum, modifiable and non-modifiable risk factors for AD treatment with a focus on prevention strategies, then research models used in AD, followed by a discussion of treatment limitations. The prevention methods can significantly slow AD evolution and are currently the best strategy possible before the advanced stages of the disease. Indeed, current drug treatments have only symptomatic effects, and disease-modifying treatments are not yet available. Drug delivery to the central nervous system remains a complex process and represents a challenge for developing therapeutic and preventive strategies. Studies are underway to test new techniques to facilitate the bioavailability of molecules to the brain. After a deep study of the literature, we find the use of soft nanoparticles, in particular nanoliposomes and exosomes, as an innovative approach for preventive and therapeutic strategies in reducing the risk of AD and solving problems of brain bioavailability. Studies show the promising role of nanoliposomes and exosomes as smart drug delivery systems able to penetrate the blood-brain barrier and target brain tissues. Finally, the different drug administration techniques for neurological disorders are discussed. One of the promising therapeutic methods is the intranasal administration strategy which should be used for preclinical and clinical studies of neurodegenerative diseases.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病,正在成为全球主要的公共卫生问题。几十年来,人们已经探索了许多治疗策略;然而,仍然没有治愈方法,重点仍然是预防。在这篇综述中,我们介绍了 AD 谱的临床和生理阶段的最新进展,以及 AD 治疗的可改变和不可改变的风险因素,重点介绍了预防策略,然后介绍了 AD 研究模型,最后讨论了治疗的局限性。预防方法可以显著减缓 AD 的进展,并且是在疾病的晚期之前目前可能的最佳策略。实际上,目前的药物治疗仅具有对症作用,而尚无针对疾病的治疗方法。药物向中枢神经系统的输送仍然是一个复杂的过程,这是开发治疗和预防策略的一个挑战。目前正在进行研究,以测试新的技术来提高分子到达大脑的生物利用度。在对文献进行深入研究后,我们发现使用软纳米颗粒,特别是纳米脂质体和外泌体,作为预防和治疗策略的一种创新方法,可降低 AD 的风险并解决大脑生物利用度的问题。研究表明,纳米脂质体和外泌体作为智能药物输送系统具有很大的应用潜力,能够穿透血脑屏障并靶向脑组织。最后,讨论了用于治疗神经退行性疾病的不同药物给药技术。有前途的治疗方法之一是鼻腔给药策略,该策略应用于神经退行性疾病的临床前和临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dae5/9697769/f219492da061/ijms-23-13954-g001.jpg

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