AMPK as a Potential Therapeutic Target for Intervertebral Disc Degeneration

Abstract

As the principal reason for low back pain, intervertebral disc degeneration (IDD) affects the health of people around the world regardless of race or region. Degenerative discs display a series of characteristic pathological changes, including cell apoptosis, senescence, remodeling of extracellular matrix, oxidative stress and inflammatory local microenvironment. As a serine/threonine-protein kinase in eukaryocytes, AMP-activated protein kinase (AMPK) is involved in various cellular processes through the modulation of cell metabolism and energy balance. Recent studies have shown the abnormal activity of AMPK in degenerative disc cells. Besides, AMPK regulates multiple crucial biological behaviors in IDD. In this review, we summarize the pathophysiologic changes of IDD and activation process of AMPK. We also attempt to generalize the role of AMPK in the pathogenesis of IDD. Moreover, therapies targeting AMPK in alleviating IDD are analyzed, for better insight into the potential of AMPK as a therapeutic target.

Effects of Fluid Shear Stress on Human Intervertebral Disc Nucleus Pulposus Cells Based on Label-Free Quantitative Proteomics

“…AMPK-induced autophagy promotes ECM synthesis and inhibits ECM degradation by regulating the expression of anabolic genes COL2A1, ACAN, and catabolic genes MMP-3, MMP-13, ADAMT-4, and ADAMT-5, thereby avoiding TBHP-induced autophagy and ECM destruction. AMPK further protects human NP cells from age-induced mitochondrial apoptosis by regulating SIRT3 [ 25 ].…”

The Use of Medical Ozone in Chronic Intervertebral Disc Degeneration Can Be an Etiological and Conservative Treatment

“…Insufficient supplement of nutrients and the accumulation of metabolites together bring about a tough microenvironment in degenerative IVD. This special local microenvironment may serve as a trigger for the overproduction of reactive oxygen species (ROS) [ 31 ]. While the microenvironment of IVDs is characterized by hypoxia due to poor vascularization, all resident disc cells (NP cells, AF cells, and CEP cells) have been demonstrated to be not anaerobic and to have oxygen-utilizing metabolic processes in vivo.…”

“…Production of ROS at high oxygen tension also correlates with reduced PG synthesis and enhanced expression of catabolic factors [ 33 ]. Meanwhile, both the contents of enzymatic antioxidants and non-enzymatic antioxidants are reduced, leading to impaired scavenging of ROS and can cause oxidative damage to DNA, lipids, and proteins and also enhance ROS production in disc cells, forming a positive feedback loop [ 31 ]. The intracellular redox homeostasis depends on a balance between ROS generation and ROS scavenging performed by nonenzymatic and enzymatic antioxidants, including glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase, ascorbic acid (vitamin C), α-tocopherol (vitamin E), and carotenoids.…”

Pharmacological Approaches to Decelerate Aging: A Promising Path

“…LKB1 expression increases via an increase in AMP to ATP ratio [ 112 , 113 ]. Upstream of the AMPK pathway also includes phosphatases such as protein phosphatase 2A (PP2A) and protein phosphatase 2C (PP2C), which avert persistent activation of AMPK by dephosphorylating AMPK [ 114 , 115 ]. Additionally, the downstream pathways of AMPK include SIRT1, TSC1/2, p53, GLUT1/GLUT4, ACC1, SREBP1, ULK1, and HuR.…”