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CD36 - 神经血管单元中的新型分子靶标。

CD36 - A novel molecular target in the neurovascular unit.

机构信息

Ultrastructural Pathology and Bioimaging Laboratory, Victor Babes Institute of Pathology, Bucharest, Romania.

Department of Cellular and Molecular Biology and Histology, School of Medicine, Carol Davila Faculty of Medicine, Bucharest, Romania.

出版信息

Eur J Neurosci. 2021 Apr;53(8):2500-2510. doi: 10.1111/ejn.15147. Epub 2021 Feb 28.

Abstract

CD36 is an integral membrane protein primarily known for its function as a fatty acid transporter, yet also playing other biological roles from lipid metabolism to inflammation modulation. These pleiotropic effects are explained by the existence of multiple different ligands and the extensive distribution in numerous cell types. Moreover, the receptor is related to various pathologies and it may prove to be a good target for prospective therapeutic strategies. In the neurovascular unit (NVU), CD36 is expressed in cells like microglia, microvascular endothelial cells, astrocytes and neurons. In the normal brain, CD36 was proven to be involved in phagocytosis of apoptotic cells, oro-sensory detection of dietary lipids, and fatty acid transport across the blood brain barrier (BBB). CD36 was also acknowledged as a potentially important player in central nervous system (CNS) disorders, such as Alzheimer Disease-associated vascular dysfunction and oxidative stress and the neuroinflammatory response in stroke. Despite continuous efforts, the therapeutic arsenal for such diseases is still scarce and there is an increasing interest in discovering new molecular targets for more specific therapeutic approaches. In this review, we summarize the role of CD36 in the normal function of the NVU and in several CNS disorders, focusing on the dysregulation of the NVU and the potential therapeutic modulation.

摘要

CD36 是一种主要作为脂肪酸转运蛋白发挥作用的完整膜蛋白,但它也在脂质代谢到炎症调节等其他生物学功能中发挥作用。这些多效性作用是由多种不同配体的存在和在许多细胞类型中的广泛分布所解释的。此外,该受体与多种病理学有关,它可能被证明是未来治疗策略的一个很好的靶点。在神经血管单元 (NVU) 中,CD36 在细胞如小胶质细胞、微血管内皮细胞、星形胶质细胞和神经元中表达。在正常大脑中,CD36 被证明参与了对凋亡细胞的吞噬作用、对膳食脂质的口感觉检测,以及脂肪酸穿过血脑屏障 (BBB) 的转运。CD36 也被认为是中枢神经系统 (CNS) 疾病的一个潜在重要参与者,如阿尔茨海默病相关的血管功能障碍和氧化应激以及中风中的神经炎症反应。尽管持续努力,针对这些疾病的治疗武器仍然稀缺,人们越来越有兴趣发现新的分子靶点,以实现更具针对性的治疗方法。在这篇综述中,我们总结了 CD36 在 NVU 的正常功能和几种 CNS 疾病中的作用,重点介绍了 NVU 的失调和潜在的治疗调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d58d/8247892/d603401ee934/EJN-53-2500-g002.jpg

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