血液诱导的ITAM信号通过激活血小板mTOR加剧了疟疾相关的神经病变发生
Irina Portier1, Frederik Denorme2, Neal D Tolley3
1Washington University, United States.
Blood
|January 26, 2026
概括
针对血小板中拉巴胺素 (mTOR) 途径的机械性标提供了针对脑疟疾 (CM) 的新策略. 删除血小板mTOR通过减少大脑血小板积累,显著改善实验性CM中的生存率.
科学领域:
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
- 传染性疾病 传染性疾病
背景情况:
- 疟疾导致全球显著的死亡率,其中大脑疟疾 (CM) 是主要的贡献者.
- 血小板在CM病变发生过程中发挥着作用,但根本的机制尚未完全理解.
- 拉巴胺素 (mTOR) 途径的机械性标是细胞过程的关键调节者,包括血小板功能.
研究的目的:
- 为了研究mTOR途径在疟疾发病过程中血小板中的作用.
- 确定针对血小板mTOR是否可以改善实验性脑疟疾 (ECM) 结果.
主要方法:
- 活化血小板 ex vivo 与感染菌的红细胞以及感染菌berghei ANKA (PbA) 的小鼠体内的活体.
- 产生了血小板特定的mTOR淘汰赛小鼠 (mTORplt-/-) 来评估ECM.
- 测量了寄生病,血小板减少,脑中的血小板沉积,脑血流和血管透性.
- 研究了海姆在激活血小板mTOR中的作用,通过ITAM信号传递和C型甲蛋白类受体2 (CLR2).
主要成果:
- 在疟疾感染期间,mTOR途径在血小板中被激活.
- mTORplt-/-小鼠表现出显著增加了ECM的存活率,独立于寄生虫病或血小板狭窄症.
- 在mTORplt-/-小鼠中观察到大脑中血小板积累减少,大脑血流改善,血管透率降低.
- 血红素激活了血小板mTOR,并且阻止这种激活降低了ECM死亡率.
结论:
- 血小板mTOR信号放大了由血红素诱导的血小板激活,有助于CM的发病.
- 删除血小板mTOR减少脑血小板沉积,阻碍疾病进展和实验性脑疟疾的死亡率.
- 向血小板mTOR代表了大脑疟疾的潜在治疗策略.
更多相关视频
09:13Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation
Published on: April 6, 2017
12.4K
05:49Procoagulant Platelet Characterization by Measuring Phosphatidylserine Exposure and Microvesicle Release from Human Purified Platelets
Published on: November 29, 2024
1.2K
相关概念视频
mTOR Signaling and Cancer Progression
4.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.7K
PI3K/mTOR/AKT Signaling Pathway
5.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.4K
What is Cell Signaling?
130.3K
Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
130.3K
Bacterial Signaling
40.6K
Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
40.6K
Cell-surface Signaling
54.2K
Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
54.2K
Endocrine Signaling
68.0K
Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
68.0K
