Chronic Inflammatory Disorders and Their Redox Control: From Molecular Mechanisms to Therapeutic Opportunities

Abstract

A chronic inflammatory disease is a condition characterized by persistent inflammation. A number of human pathologies fall into this category, and a great deal of research has been conducted to learn more about their characteristics and underlying mechanisms. In many cases, a genetic component has been identified, but also external factors like food, smoke, or environmental pollutants can significantly contribute to worsen their symptoms. Accumulated evidence clearly shows that chronic inflammatory diseases are subjected to a redox control. Here, we shall review the identity, source, regulation, and biological activity of redox molecules, to put in a better perspective their key-role in cancer, diabetes, cardiovascular diseases, atherosclerosis, chronic obstructive pulmonary diseases, and inflammatory bowel diseases. In addition, the impact of redox species on autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and celiac disease) and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis) will be discussed, along with their potential therapeutic implications as novel drugs to combat chronic inflammatory disorders.

Acacia ferrugineainhibits inflammation by regulating inflammatory iNOS and COX-2

“…It is known that inflammation-related proteins including COX-2, iNOS, matrix metalloproteinase (MMP)-9 and cytosolic phospholipase A 2 (cPLA 2 ) are associated with oxidative stress (excess production of reactive oxygen species [ROS]) induced by pro-inflammatory agents, include several cytokines, peptides and peroxidants (Chiurchiu & MacCarrone, 2011;Lee & Yang 2012). Apart from a role in inducing oxidative stress, ROS can cause deleterious effects due to reactivity with DNA, resulting in altered DNA structures, decreased DNA repair; these agents can also lead to up-regulation of cell signaling cascades including those associated with mitogen-activated protein kinases (MAPK) and growth factor kinase.…”

Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?

“…The piecemeal loss of melanin-containing nigral neurons leads to aberrant dopaminergic transmission, with tremor emerging as a consequence of subthalamic overactivity [64][65][66][67][68][69]. The increase in the levels of endocannabinoids and alteration in both CB 1 R and CB 2 R expression in different stages of PD opens the possibility of manipulation of receptor function in the management of disease [64,70].…”

“…There is much anecdotal evidence that patients self-medicate with marijuana with the intention of palliating pain, tremor, spasticity, ataxia, and other symptoms associated with MS, an autoimmune disease typified by demyelination and remyelination, and associated with neuroaxonal damage and inflammation [67,69,85,86]. More recent controlled studies, both in animal models of MS and in humans, have begun to validate these preclinical and uncontrolled observations.…”

Neuroinflammation: Peripheral and Neurogenic Underlying Processes

“…Microglia and astrocytes release inflammatory mediators in response to oxidative stress (Cahill-Smith and Li, 2014;Chiurchiu and Maccarrone, 2011;Fuller et al, 2010). Reactive oxygen species (ROS) can activate inflammatory responses in the CNS by stimulating redox-sensitive transcription factors, including the nuclear factor κB and activator protein-1 (AP-1) (Chiurchiu and Maccarrone, 2011).…”

“…Microglia and astrocytes release inflammatory mediators in response to oxidative stress (Cahill-Smith and Li, 2014;Chiurchiu and Maccarrone, 2011;Fuller et al, 2010). Reactive oxygen species (ROS) can activate inflammatory responses in the CNS by stimulating redox-sensitive transcription factors, including the nuclear factor κB and activator protein-1 (AP-1) (Chiurchiu and Maccarrone, 2011). These factors increase the synthesis of inflammatory mediators such as 5-lipoxygenase (5LOX); the nitric oxide synthase (NOS) isoforms; cytokines (particularly TNF-α); chemokines; immunoglobulin Fc receptors (FcγR); adhesion molecules like P-and E-selectine, VCAM-1, and ICAM-1 (Sandireddy et al, 2014), as well as matrix metalloproteinases (MMPs), cytosolic phospholipase A2 (cPLA2), and cyclooxygenase-2 (COX-2) (Hsieh and Yang, 2013); all of them promote an inflammatory environment.…”