In summary using the Nurr

In summary, using the Nurr1 agonist AQ we first showed that Nurr1 plays an important role in the regulation of adult hippocampal neurogenesis. AQ may increase adult hippocampal neurogenesis via, in part, an up-regulated phosphorylation of Akt and ERK1/2. Moreover, the Nurr1 agonist enhances both short- and long-term memory, the cognitive processes strongly associated with adult hippocampal neurogenesis. Taken together, these findings suggest that Nurr1 can be used as a therapeutic target for the treatment of memory disorders or neurodegenerative diseases associated with impaired adult neurogenesis. In conclusion, AQ is a viable candidate as a pharmacological KN-93 hydrochloride cost for treating the impaired memory functions described in many cognitive diseases. The following are the supplementary data related to this article.
Acknowledgment This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2015R1C1A1A01052732); a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C0816) to M.M. and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science (NRF-2014R1A1A2058316) to H.C.
Introduction Deficits in pancreatic cell function are a major cause of human diseases, including diabetes and pancreatitis. In particular, diabetes occurs as a consequence of defects of insulin producing β-cells in the pancreatic islets. Patients require exogenous insulin treatment to ameliorate the disease, but glycemic control can be difficult. The most definitive treatment for the disease is allogeneic pancreas/islet transplantation, which provides a self-regulating insulin source (Robertson et al., 2000). However, this method is largely limited by the severe shortage of transplantable material. Additionally, patients require life-long immunosuppression after transplantation, which increases the risk of infection and certain types of cancer (Ryan et al., 2005). Therefore, a long-term goal in the field is to generate autologous insulin-producing cells for β cell replacement therapy. One approach to generate insulin-producing cells is through differentiation of embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), in which cultured ESCs or iPSCs are induced through a series of steps designed to mimic the developmental process. Pancreatic endocrine progenitor cells have been produced using this approach in vitro and these cells further mature 3–4months after transplantation and eventually reverse chemical-induced diabetes in animal models (D\'Amour et al., 2006; Kroon et al., 2008). However, not until recently have glucose-responsive insulin-secreting cells been generated in vitro. Through small molecule screenings, a stage-wise differentiation protocol was developed to scalable produce glucose-responsive insulin-producing cells in vitro (Pagliuca et al., 2014; Rezania et al., 2014). The new protocols produce an average of 33–50% insulin+/NKX6.1+ cells. These cells showed key β cell features and were able to respond to consecutive glucose challenges in vitro. However, the in vitro differentiation regimen usually takes more than one month starting from ESCs or iPSCs and concerns of immunogenicity and teratoma formation of transplanted cells still exist (Ben-David and Benvenisty, 2011). Patient-specific insulin-producing cells can be produced through direct lineage conversion from readily available cells in the patient. This method aims at direct transdifferentiation to generate cells of interest by forced expression of fate-specifying transcription factors. Efforts have been made in converting pancreatic acinar cells (Li et al., 2014a; Zhou et al., 2008), pancreatic ductal cells (Lee et al., 2013), endocrine α cells (Bramswig et al., 2013) and liver cells (Banga et al., 2012, 2014; Meivar-Levy and Ferber, 2015) into insulin-producing cells. However, these cell types are generally not easily accessed from patients. Cells generated using this approach usually do not completely recapitulate the function of bona fide β cells (Cahan et al., 2014) and their reprogramming extent is not fully characterized.