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本文引用的文献

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Cardiovascular disease and mTOR signaling.心血管疾病与 mTOR 信号通路。
Trends Cardiovasc Med. 2011 Jul;21(5):151-5. doi: 10.1016/j.tcm.2012.04.005.
2
Autophagy intersections with conventional and unconventional secretion in tissue development, remodeling and inflammation.自噬与传统和非传统分泌在组织发育、重塑和炎症中的交汇。
Trends Cell Biol. 2012 Aug;22(8):397-406. doi: 10.1016/j.tcb.2012.04.008. Epub 2012 Jun 5.
3
Mammalian target of rapamycin signaling in diabetic cardiovascular disease.雷帕霉素靶蛋白信号通路在糖尿病性心血管疾病中的作用。
Cardiovasc Diabetol. 2012 Jul 16;11:45. doi: 10.1186/1475-2840-11-45.
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The many facets of cell injury: angiogenesis to autophagy.细胞损伤的多个方面:从血管生成到自噬
Curr Neurovasc Res. 2012 May;9(2):83-4. doi: 10.2174/156720212800410911.
5
WISP1 (CCN4) autoregulates its expression and nuclear trafficking of β-catenin during oxidant stress with limited effects upon neuronal autophagy.在氧化应激条件下,WISP1(CCN4)通过自调控其表达和β-catenin 的核转位,对神经元自噬的影响有限。
Curr Neurovasc Res. 2012 May;9(2):91-101. doi: 10.2174/156720212800410858.
6
Autophagy induced by resveratrol prevents human prion protein-mediated neurotoxicity.白藜芦醇诱导的自噬可预防人朊病毒蛋白介导的神经毒性。
Neurosci Res. 2012 Jun;73(2):99-105. doi: 10.1016/j.neures.2012.03.005. Epub 2012 Mar 23.
7
NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity.NVP-BEZ235 和 NVP-BGT226 是双重磷脂酰肌醇 3-激酶/雷帕霉素哺乳动物靶蛋白抑制剂,可增强肿瘤和内皮细胞的放射敏感性。
Radiat Oncol. 2012 Mar 27;7:48. doi: 10.1186/1748-717X-7-48.
8
GLP1-derived nonapeptide GLP1(28-36)amide protects pancreatic β-cells from glucolipotoxicity.GLP1 衍生的九肽 GLP1(28-36)酰胺可保护胰岛 β 细胞免受糖脂毒性的损害。
J Endocrinol. 2012 May;213(2):143-54. doi: 10.1530/JOE-11-0328. Epub 2012 Mar 13.
9
The role of canonical WNT signaling pathway in oral carcinogenesis: a comprehensive review.经典 WNT 信号通路在口腔癌发生中的作用:全面综述。
Anticancer Res. 2012 Mar;32(3):873-8.
10
Prevention of β-amyloid degeneration of microglia by erythropoietin depends on Wnt1, the PI 3-K/mTOR pathway, Bad, and Bcl-xL.促红细胞生成素对小胶质细胞β-淀粉样蛋白变性的预防作用依赖于Wnt1、PI 3-K/mTOR信号通路、Bad和Bcl-xL。
Aging (Albany NY). 2012 Mar;4(3):187-201. doi: 10.18632/aging.100440.

通过细胞凋亡和自噬的新途径靶向疾病。

Targeting disease through novel pathways of apoptosis and autophagy.

机构信息

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.

出版信息

Expert Opin Ther Targets. 2012 Dec;16(12):1203-14. doi: 10.1517/14728222.2012.719499. Epub 2012 Aug 27.

DOI:10.1517/14728222.2012.719499
PMID:22924465
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3500415/
Abstract

INTRODUCTION

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.

AREAS COVERED

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.

EXPERT OPINION

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.

摘要

简介

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。

涵盖领域

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。

专家意见

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。