Netrin-1 in Post-stroke Neuroprotection: Beyond Axon Guidance Cue

Background: Stroke, especially ischemic stroke, is a leading disease associated with death and long-term disability with limited therapeutic options. Neuronal death caused by vascular impairment, programmed cell death and neuroinflammation has been proven to be associated with increased stroke severity and poor stroke recovery. In light of this, a development of neuroprotective drugs targeting injured neurons is urgently needed for stroke treatment. Netrin-1, known as a bifunctional molecule, was originally described to mediate the repulsion or attraction of axonal growth by interacting with its different receptors. Importantly, accumulating evidence has shown that netrin-1 can manifest its beneficial functions to brain tissue repair and neural regeneration in different neurological disease models. Objective: In this review, we focus on the implications of netrin-1 and its possibly involved pathways on neuroprotection after ischemic stroke, through which a better understanding of the underlying mechanisms of netrin-1 may pave the way to novel treatments. Methods: Peer-reviewed literature was recruited by searching databases of PubMed, Scopus, Embase, and Web of Science till the year 2021. Conclusion: There has been certain evidence to support the neuroprotective function of netrin-1 by regulating angiogenesis, autophagy, apoptosis and neuroinflammation after stroke. Netrin-1 may be a promising drug candidate in reducing stroke severity and improving outcomes.