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从生长因子衍生的肽治疗阿尔茨海默病。

Peptides Derived from Growth Factors to Treat Alzheimer's Disease.

机构信息

Laboratory of Cell-Biomaterial Biohybrid Systems, Department of Chemical and Biotechnological Engineering, 2500 Boulevard Université, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.

Département de Pharmacologie-Physiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.

出版信息

Int J Mol Sci. 2021 Jun 4;22(11):6071. doi: 10.3390/ijms22116071.

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood-brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

摘要

阿尔茨海默病(AD)是一种破坏性的神经退行性疾病,其特征是与记忆相关的大脑结构中的神经元逐渐丧失。AD 的典型特征是胆碱能系统失调、淀粉样斑块积累和神经纤维缠结。不幸的是,目前的治疗方法无法治愈甚至延缓疾病的进展。因此,出现了新的治疗策略,例如外源性给予神经营养因子(例如 NGF 和 BDNF),这些因子在 AD 中不足或失调。然而,它们穿过血脑屏障的能力低和高昂的成本目前限制了它们的使用。为了克服这些限制,已经开发了模拟这些生长因子结合受体位点的短肽。这些肽可以靶向涉及神经元存活、分化和/或维持的选择性信号通路。本综述重点介绍了生长因子及其衍生肽作为 AD 潜在治疗方法的研究进展。它描述了(1)生长因子在大脑中的生理功能、其神经元信号通路以及在 AD 中的改变;(2)开发源自生长因子的肽的策略及其模拟天然蛋白作用的能力;以及(3)这些分子作为 AD 治疗方法的新进展和潜力,以及它们的局限性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f23/8200100/a45aecc9d273/ijms-22-06071-g001.jpg

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