哺乳动物雷帕霉素靶蛋白：神经系统治疗的新靶点美国神经科学细胞及分子信号研究实验室Kenneth Maiese博士，在《中国神经再生研究》（英文版）杂志2015年10卷第4期探讨了如何通过生长因子、Wnt信号及WISP1和干细胞组织防止糖尿病神经系统并发症的问题。
营养因子，如胰岛素样生长因子-1、成纤维细胞生长因子、表皮生长因子和促红细胞生成素，可以通过控制氧化应激和糖尿病中葡萄糖稳态防止神经元死亡。
有趣的是最近的研究也表明，细胞因子和生长因子促红细胞生成素通过Wnt信号保护间充质干细胞防止血管损伤死亡有关的途径，促进神经系统免疫细胞起到保护作用。
通过独立的途径，Wnt信号和WISP1通过促进干细胞的生长和迁移，增加胰细胞增殖，从而导致新的血管生长，修复糖尿病伤口，并控制关键的程序性细胞死亡途径促进糖尿病期间保护神经系统中的细胞凋亡和自噬。
在下游区，Wnt信号和WISP1通过雷帕霉素和AMP途径维持葡萄糖稳态和正常代谢活化的蛋白激酶。
Maiese博士还强调了通过注意“这些生物系统的活化程度是通过设计是营养因子、Wnt信号、WISP1治疗糖尿病保护神经系统时所必须考虑的。
例如，Wnt信号、WISP1和生长因子可导致如血管渗漏的视网膜和视力损害甚至癌症。
总之，神经系统生长因子、Wnt信号和WISP1具有治疗糖尿病的并发症的广阔前景，然而，如何精确应用这些途径的靶点成功的保护修复神经系统及神经元的功能仍值得探讨。
Article: "Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease" by Kenneth Maiese (Cellular and Molecular Signaling, Newark, New Jersey 07101, USA)Maiese K (2015) Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease. Neural Regen Res 10(4):518-528.欲获更多资讯：文章全文请见：Neural Regen ResNew Prospects for Targeting Diabetes Mellitus with Trophic Factors, Wnt, and WISP SUMMARYDiabetes mellitus (DM) affects almost 350 million individuals throughout the world and leads to significant disability in the nervous system involving dementia, stroke, neuropathy, and retinal disease. To combat these detrimental effects of DM, new avenues of discovery are being pursued that target novel growth factors and specific cellular pathways of Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1), and stem cells to block neuronal death and potentially lead to reparative processes in the nervous system.NEWS RELEASEDr. Kenneth Maiese, an expert in cellular signaling and a physician scientist, explores in the journal Neural Regeneration Research(Vol. 10, No. 4, 2015) how novel targeting with growth factors, Wnt, WISP1, and stem cell tissue regeneration may offer new strategies to prevent the complications of DM in the nervous system. Trophic factors that include insulin-like growth factor-1 (IGF-1), fibroblast growth factor (FGF), epidermal growth factor (EGF), anderythropoietin (EPO) can each control glucose homeostasis and prevent neurons from dying during the insults of oxidative stress and DM. Interestingly, recent studies also have revealed that the cytokine and growth factor EPO uses Wnt signaling to the preserve mesenchymal stem cells, protect against vascular injury, block “death-related” pathways, and promote immune cell protection of the nervous system. Through independent pathways, Wnt signaling and WISP1 promote protection in the nervous system during DM by fostering stem cell growth and migration, increasing pancreatic -cell proliferation, leading to new blood vessel growth, repairing diabetic wounds, and controlling critical programmed cell death pathways of apoptosis and autophagy. Further downstream, Wnt and WISP1 assist to maintain glucose homeostasis and normal metabolism through the pathways of the mechanistic target of rapamycin (mTOR) and AMP activated protein kinase (AMPK). Maiese also emphasizes the complexity of trophic factors, Wnt, and WISP1 in designing strategies to protect the nervous system by noting “the degree of activation of these biological systems is an important consideration in developing therapies for DM”. For example, Wnt, WISP1, and growth factors can lead to complications such as vascular leakage in the retina and impair vision as well as lead to cancer is some systems of the body. Pathways such as AMPK also have the potential to lead to the death of pancreatic islet cells under some circumstances. Overall the prospects for developing new therapeutic strategies for the complications of DM in the nervous system with growth factors, Wnt, and WISP1 are met with great enthusiasm but require precise targeting of these pathways to bear clinical success for neuronal protection, repair, and regeneration in the nervous system.Article: "Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease" by Kenneth Maiese (Cellular and Molecular Signaling, Newark, New Jersey 07101, USA)Maiese K (2015) Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease. Neural Regen Res 10(4):518-528.。