Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Hainan Medical University, Haikou 571199, China.
Department of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Int J Mol Sci. 2022 Aug 25;23(17):9648. doi: 10.3390/ijms23179648.
Stroke is among the leading causes of death and disability worldwide. However, despite long-term research yielding numerous candidate neuroprotective drugs, there remains a lack of effective neuroprotective therapies for ischemic stroke patients. Among the factors contributing to this deficiency could be that single-target therapy is insufficient in addressing the complex and extensive mechanistic basis of ischemic brain injury. In this context, lipids serve as an essential component of multiple biological processes and play important roles in the pathogenesis of numerous common neurological diseases. Moreover, in recent years, fatty acid-binding proteins (FABPs), a family of lipid chaperone proteins, have been discovered to be involved in the onset or development of several neurodegenerative diseases, including Alzheimer's and Parkinson's disease. However, comparatively little attention has focused on the roles played by FABPs in ischemic stroke. We have recently demonstrated that neural tissue-associated FABPs are involved in the pathological mechanism of ischemic brain injury in mice. Here, we review the literature published in the past decade that has reported on the associations between FABPs and ischemia and summarize the relevant regulatory mechanisms of FABPs implicated in ischemic injury. We also propose candidate FABPs that could serve as potential therapeutic targets for ischemic stroke.
中风是全球范围内导致死亡和残疾的主要原因之一。然而,尽管长期的研究产生了许多候选神经保护药物,但仍然缺乏有效的神经保护疗法来治疗缺血性中风患者。造成这种不足的因素之一可能是,单一靶点治疗不足以解决缺血性脑损伤的复杂和广泛的机制基础。在这种情况下,脂质是多种生物过程的重要组成部分,在许多常见神经疾病的发病机制中发挥着重要作用。此外,近年来,脂肪酸结合蛋白(FABP)作为脂质伴侣蛋白家族,已被发现与几种神经退行性疾病的发生或发展有关,包括阿尔茨海默病和帕金森病。然而,人们对 FABP 在缺血性中风中的作用关注甚少。我们最近证明,神经组织相关 FABP 参与了小鼠缺血性脑损伤的病理机制。在这里,我们回顾了过去十年中发表的文献,这些文献报道了 FABP 与缺血之间的关联,并总结了 FABP 参与缺血性损伤的相关调节机制。我们还提出了候选 FABP,它们可能成为缺血性中风的潜在治疗靶点。