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甲状腺素胺（TAMs）向脑内的递送：一项初步研究。

Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study.

机构信息

Smart Bio-Interfaces, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy.

The Biorobotics Institute, Scuola Superiore Sant'Anna, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy.

出版信息

Molecules. 2021 Mar 14;26(6):1616. doi: 10.3390/molecules26061616.

DOI:10.3390/molecules26061616
PMID:33799468
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7999687/
Abstract

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood-brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.

摘要

最近的报告强调了甲状腺素胺（TAMs）的重要神经保护作用，TAMs 是一类内源性甲状腺激素衍生物。特别是，3-碘甲状腺素胺（T1AM）已被证明在通过调节能量代谢和神经功能在小鼠中发挥多效性作用在神经退行性变中发挥作用。然而，T1AM 的药理反应可能受到组织代谢的影响，已知组织代谢会将 T1AM 转化为其代谢产物 3-碘甲状腺乙酸（TA1）。目前，有几个研究小组正在研究 T1AM 全身给药的药理作用，以期寻找治疗代谢和神经退行性疾病（NDD）等相关疾病的新疗法。开发用于治疗 NDD 的新药的一个关键方面是要了解它们在大脑中的分布，这与它们穿过血脑屏障（BBB）的能力密切相关。为此，在本研究中，我们使用永生化的小鼠脑内皮细胞系 bEnd.3 开发了 BBB 的体外模型，并评估了 T1AM 和 TA1 的通透性。两种药物均以 1µM 剂量给药，通过高效液相色谱-质谱联用进行检测。我们的结果表明，T1AM 能够有效地穿过 BBB，而 TA1 几乎完全缺乏这种特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/254585328a10/molecules-26-01616-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/0d9829cbe7fa/molecules-26-01616-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/cd615e441d5f/molecules-26-01616-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/e2467d952db6/molecules-26-01616-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/05552ef2f81c/molecules-26-01616-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/675d2f40ec77/molecules-26-01616-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/5af5bae16fd7/molecules-26-01616-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/4033e669aa26/molecules-26-01616-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/706bae6a46f6/molecules-26-01616-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/1b62c7849c2a/molecules-26-01616-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/254585328a10/molecules-26-01616-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/0d9829cbe7fa/molecules-26-01616-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/cd615e441d5f/molecules-26-01616-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/e2467d952db6/molecules-26-01616-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/05552ef2f81c/molecules-26-01616-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/675d2f40ec77/molecules-26-01616-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/5af5bae16fd7/molecules-26-01616-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/4033e669aa26/molecules-26-01616-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/706bae6a46f6/molecules-26-01616-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/1b62c7849c2a/molecules-26-01616-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/7999687/254585328a10/molecules-26-01616-sch003.jpg

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