The PI3K/Akt pathway: a critical player in intervertebral disc degeneration.

Zhi-Hua Ouyang,Guo-Hua Lv,Wen-Jun Wang,Bing Wang,Yi-Guo Yan

doi:10.18632/oncotarget.18628

Abstract

Intervertebral disc degeneration (IDD) is thought to be the primary cause of low back pain, a severe public health problem worldwide. Current therapy for IDD aims to alleviate the symptoms and does not target the underlying pathological alternations within the disc. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway protects against IDD, which is attributed to increase of ECM content, prevention of cell apoptosis, facilitation of cell proliferation, induction or prevention of cell autophagy, alleviation of oxidative damage, and adaptation of hypoxic microenvironment. In the current review, we summarize recent progression on activation and negative regulation of the PI3K/Akt signaling pathway, and highlight its impact on IDD. Targeting this pathway could become an attractive therapeutic strategy for IDD in the near future.

Highlights

Low back pain (LBP) is a major public health problem worldwide, resulting in a huge socioeconomic burden [1,2,3,4]
Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway protects against Intervertebral disc degeneration (IDD), which is attributed to increase of extracellular matrix (ECM) content, prevention of cell apoptosis, facilitation of cell proliferation, induction or prevention of cell autophagy, alleviation of oxidative damage, and adaptation of hypoxic microenvironment
Activated PI3K/Akt pathway has been shown to protect against disc degeneration through multiple mechanisms, there are a number of outstanding issues that need to be addressed

Summary

Introduction

Low back pain (LBP) is a major public health problem worldwide, resulting in a huge socioeconomic burden [1,2,3,4]. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway protects against IDD, which is attributed to increase of ECM content, prevention of cell apoptosis, facilitation of cell proliferation, induction or prevention of cell autophagy, alleviation of oxidative damage, and adaptation of hypoxic microenvironment. Thereafter, activated Akt interacts with downstream target proteins to regulate multiple biological processes, including apoptosis, autophagy and cell cycle progression (Figure 1).

Results

Conclusion