The Role and Regulatory Mechanism of Hippo Signaling Components in the Neuronal System

Abstract

The Hippo signaling pathway, an evolutionarily conserved protein kinase cascade, plays a critical role in controlling organ size, cancer development, and tissue regeneration. Recently, mounting evidence has suggested that Hippo signaling also has an important role in regulating immunity, including innate and adaptive immune activation. In the neuronal system, Our laboratory results, together with those from other studies, demonstrate that the Hippo signaling pathway is involved in neuroinflammation, neuronal cell differentiation, and neuronal death. In the present review, we summarize the recent findings pertaining to the function and regulatory mechanism of Hippo signaling components in the neuronal system, implicating the potential of Hippo signaling as a therapeutic target for the treatment of neuronal system diseases.

Targeting connexin 43 provides anti-inflammatory effects after intracerebral hemorrhage injury by regulating YAP signaling

“…Recently, mounting evidence has shown the important role of Hippo/YAP signaling in CNS homeostasis. Dysfunction of Hippo/YAP signaling contributes to negative proapoptotic and proinflammatory effects in CNS diseases [ 15 ]. During cerebral ischemic injury, YAP deletion aggravates BBB and astrocyte damage.…”

“…Unlike other core proteins of the Hippo signaling pathway (MSTs, LATS, and TAZ), YAP has been suggested to be strictly located in astrocytes and neural stem cells. Specifically, members of the TEAD family, including TEAD1, TEAD2, and TEAD3, are the core transcription factors of YAP in the nucleus and are expressed in astrocytes [ 15 ]. YAP, the transcriptional coactivator of Hippo signaling, has largely been studied for its role in the immune response and as a potential transcriptional regulation of the tumor checkpoint receptor PD-1 [ 16 , 17 ].…”

Multi‐Tissue Multi‐Omics Nutrigenomics Indicates Context‐Specific Effects of Docosahexaenoic Acid on Rat Brain

“…Recent studies implicate its role in neural functions, such as neuroinflammation and neuronal cell death. [37] In hypothalamus, Rap1 signaling pathway was also captured, which is involved in neuronal connectivity, [38] hypothalamic inflammation, and leptin sensitivity. [39] Agreeing with the transcriptome-level findings, the DNA methylation loci affected by DHA under the two dietary conditions were also drastically different.…”

Targeting Connexin43 provides anti-inflammatory effects after intracerebral hemorrhage injury by regulating YAP signaling

“…Early studies showed that abnormal Hippo signaling contributes to the development of tumors [61].Recently, mounting evidence has shown the important role of Hippo/YAP signaling in CNS homeostasis. Dysfunction of Hippo/YAP signaling contributes to negative proapoptotic and proin ammatory effects in CNS diseases [16]. During cerebral ischemic injury,YAP deletion aggravates BBB and astrocyte damage.MST1,another important regulator of YAP in the Hippo pathways, is overactivated in a model of ICH, and knocking down MST1 mitigates in ammatory reactions and neuronal cell death [62].…”