Fatty Acid-Binding Proteins: Their Roles in Ischemic Stroke and Potential as Drug Targets

Int J Mol Sci. 2022 Aug 25;23(17):9648. doi: 10.3390/ijms23179648.

Abstract

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.

Keywords: fatty acid-binding protein; ischemic cascade; ischemic stroke; mitochondria; neurovascular unit.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain Injuries* / metabolism
  • Brain Ischemia* / metabolism
  • Fatty Acid-Binding Proteins / metabolism
  • Ischemic Stroke* / drug therapy
  • Mice
  • Stroke* / metabolism

Substances

  • Fatty Acid-Binding Proteins

Grants and funding

This research was supported in part by the Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and Development, AMED [grant numbers JP20dm0107071] to K.F. and Japan Society for the Promotion of Science, KAKENHI (22K06644), Takeda Science Foundation and Smoking Research Foundation to I.K.