New Jersey Health Sciences University, Cancer Institute of New Jersey, Laboratory of Cellular and Molecular Signaling, F 1220, 205 South Orange Avenue, Newark, New Jersey 07101, USA.
Expert Opin Ther Targets. 2012 Dec;16(12):1203-14. doi: 10.1517/14728222.2012.719499. Epub 2012 Aug 27.
Apoptosis and autophagy impact cell death in multiple systems of the body. Development of new therapeutic strategies that target these processes must address their complex role during developmental cell growth as well as during the modulation of toxic cellular environments.
Novel signaling pathways involving Wnt1-inducible signaling pathway protein 1 (WISP1), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), β-catenin and mammalian target of rapamycin (mTOR) govern apoptotic and autophagic pathways during oxidant stress that affect the course of a broad spectrum of disease entities including Alzheimer's disease, Parkinson's disease, myocardial injury, skeletal system trauma, immune system dysfunction and cancer progression. Implications of potential biological and clinical outcome for these signaling pathways are presented.
The CCN family member WISP1 and its intimate relationship with canonical and non-canonical wingless signaling pathways of PI3K, Akt1, β-catenin and mTOR offer an exciting approach for governing the pathways of apoptosis and autophagy especially in clinical disorders that are currently without effective treatments. Future studies that can elucidate the intricate role of these cytoprotective pathways during apoptosis and autophagy can further the successful translation and development of these cellular targets into robust and safe clinical therapeutic strategies.
细胞凋亡和自噬会影响体内多个系统的细胞死亡。开发靶向这些过程的新治疗策略必须解决它们在发育细胞生长过程中以及在调节有毒细胞环境过程中的复杂作用。
涉及 Wnt1 诱导信号通路蛋白 1(WISP1)、磷酸肌醇 3-激酶(PI3K)、蛋白激酶 B(Akt)、β-连环蛋白和雷帕霉素靶蛋白(mTOR)的新信号通路在氧化应激期间调控细胞凋亡和自噬途径,这些途径会影响包括阿尔茨海默病、帕金森病、心肌损伤、骨骼系统创伤、免疫系统功能障碍和癌症进展在内的广泛疾病实体的病程。介绍了这些信号通路的潜在生物学和临床结果的意义。
富含半胱氨酸的酸性分泌蛋白(CCN)家族成员 WISP1 及其与 PI3K、Akt1、β-连环蛋白和 mTOR 的经典和非经典 Wnt 信号通路的密切关系为调控细胞凋亡和自噬途径提供了令人兴奋的方法,特别是在目前尚无有效治疗方法的临床疾病中。未来的研究可以阐明这些细胞保护途径在细胞凋亡和自噬过程中的复杂作用,从而将这些细胞靶点成功转化为强大且安全的临床治疗策略。