Menet Romain, Lecordier Sarah, ElAli Ayman
Neuroscience Axis, Research Center of CHU de Québec - Université Laval, Quebec City, QC, Canada.
Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, Quebec City, QC, Canada.
Front Physiol. 2020 Sep 18;11:565667. doi: 10.3389/fphys.2020.565667. eCollection 2020.
The Wnt pathway, which comprises the canonical and non-canonical pathways, is an evolutionarily conserved mechanism that regulates crucial biological aspects throughout the development and adulthood. Emergence and patterning of the nervous and vascular systems are intimately coordinated, a process in which Wnt pathway plays particularly important roles. In the brain, Wnt ligands activate a cell-specific surface receptor complex to induce intracellular signaling cascades regulating neurogenesis, synaptogenesis, neuronal plasticity, synaptic plasticity, angiogenesis, vascular stabilization, and inflammation. The Wnt pathway is tightly regulated in the adult brain to maintain neurovascular functions. Historically, research in neuroscience has emphasized essentially on investigating the pathway in neurodegenerative disorders. Nonetheless, emerging findings have demonstrated that the pathway is deregulated in vascular- and traumatic-mediated brain injuries. These findings are suggesting that the pathway constitutes a promising target for the development of novel therapeutic protective and restorative interventions. Yet, targeting a complex multifunctional signal transduction pathway remains a major challenge. The review aims to summarize the current knowledge regarding the implication of Wnt pathway in the pathobiology of ischemic and hemorrhagic stroke, as well as traumatic brain injury (TBI). Furthermore, the review will present the strategies used so far to manipulate the pathway for therapeutic purposes as to highlight potential future directions.
Wnt信号通路包括经典和非经典通路，是一种在进化上保守的机制，在整个发育和成年期调节关键的生物学过程。神经和血管系统的出现与模式形成密切协调，Wnt信号通路在这一过程中发挥着特别重要的作用。在大脑中，Wnt配体激活细胞特异性表面受体复合物，以诱导细胞内信号级联反应，调节神经发生、突触形成、神经元可塑性、突触可塑性、血管生成、血管稳定和炎症。Wnt信号通路在成人大脑中受到严格调控，以维持神经血管功能。从历史上看，神经科学研究主要侧重于研究该通路在神经退行性疾病中的作用。尽管如此，新出现的研究结果表明，该通路在血管性和创伤性脑损伤中失调。这些发现表明，该通路是开发新型治疗性保护和恢复性干预措施的一个有前景的靶点。然而，针对一个复杂的多功能信号转导通路仍然是一项重大挑战。本综述旨在总结目前关于Wnt信号通路在缺血性和出血性中风以及创伤性脑损伤（TBI）病理生物学中的作用的知识。此外，本综述将介绍迄今为止用于操纵该通路以达到治疗目的的策略，以突出潜在的未来方向。
