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四聚体甲状腺素运载蛋白作为对抗阿尔茨海默病的保护因子。

Tetrameric Transthyretin as a Protective Factor Against Alzheimer's Disease.

作者信息

Corino Camilla, Aimo Alberto, Luigetti Marco, Ciccone Lidia, Ferrari Chen Yu Fu, Panichella Giorgia, Musetti Veronica, Castiglione Vincenzo, Vergaro Giuseppe, Emdin Michele, Franzini Maria

机构信息

Health Sciences Interdisciplinary Center, Scuola Superiore Sant'Anna, Piazza Martiri Della Libertà 33, 56127, Pisa, Italy.

Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

出版信息

Mol Neurobiol. 2025 Mar;62(3):2945-2954. doi: 10.1007/s12035-024-04442-8. Epub 2024 Aug 27.

Abstract

Transthyretin (TTR) is a tetrameric protein traditionally recognized for its role in transporting thyroxine and retinol. Recent research has highlighted the potential neuroprotective functions of TTR in the setting of Alzheimer's disease (AD), which is the most common form of dementia and is caused by the deposition of amyloid beta (Aβ) and the resulting cytotoxic effects. This paper explores the mechanisms of TTR protective action, including its interaction with Aβ to prevent fibril formation and promote Aβ clearance from the brain. It also synthesizes experimental evidence suggesting that enhanced TTR stability may mitigate neurodegeneration and cognitive decline in AD. Potential therapeutic strategies such as small molecule stabilizers of TTR are discussed, highlighting their role in enhancing TTR binding to Aβ and facilitating its clearance. By consolidating current knowledge and proposing directions for future research, this review aims to underscore the significance of TTR as a neuroprotective factor in AD and the potential implications for future research.

摘要

转甲状腺素蛋白(TTR)是一种四聚体蛋白,传统上认为其在运输甲状腺素和视黄醇方面发挥作用。最近的研究突出了TTR在阿尔茨海默病(AD)背景下的潜在神经保护功能,AD是最常见的痴呆形式,由β淀粉样蛋白(Aβ)沉积及由此产生的细胞毒性作用引起。本文探讨了TTR保护作用的机制,包括其与Aβ相互作用以防止纤维形成并促进Aβ从脑中清除。它还综合了实验证据,表明增强TTR稳定性可能减轻AD中的神经退行性变和认知衰退。讨论了诸如TTR小分子稳定剂等潜在治疗策略,强调了它们在增强TTR与Aβ结合及促进其清除方面的作用。通过整合当前知识并为未来研究提出方向,本综述旨在强调TTR作为AD中神经保护因子的重要性以及对未来研究的潜在影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e0/11790689/1862c6054d39/12035_2024_4442_Fig1_HTML.jpg

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