The Role of Interleukin-18, Oxidative Stress and Metabolic Syndrome in Alzheimer’s Disease

Abstract

The role of interleukins (ILs) and oxidative stress (OS) in precipitating neurodegenerative diseases including sporadic Alzheimer’s disease (AD), requires further clarification. In addition to neuropathological hallmarks—extracellular neuritic amyloid-β (Aβ) plaques, neurofibrillary tangles (NFT) containing hyperphosphorylated tau and neuronal loss—chronic inflammation, as well as oxidative and excitotoxic damage, are present in the AD brain. The pathological sequelae and the interaction of these events during the course of AD need further investigation. The brain is particularly sensitive to OS, due to the richness of its peroxidation-sensitive fatty acids, coupled with its high oxygen demand. At the same time, the brain lack robust antioxidant systems. Among the multiple mechanisms and triggers by which OS can accumulate, inflammatory cytokines can sustain oxidative and nitrosative stress, leading eventually to cellular damage. Understanding the consequences of inflammation and OS may clarify the initial events underlying AD, including in interaction with genetic factors. Inflammatory cytokines are potential inducers of aberrant gene expression through transcription factors. Susceptibility disorders for AD, including obesity, type-2 diabetes, cardiovascular diseases and metabolic syndrome have been linked to increases in the proinflammatory cytokine, IL-18, which also regulates multiple AD related proteins. The association of IL-18 with AD and AD-linked medical conditions are reviewed in the article. Such data indicates that an active lifestyle, coupled to a healthy diet can ameliorate inflammation and reduce the risk of sporadic AD.

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer’s Like Pathology in Mice Brain

“…We also found that HFD-fed mice showed significantly increased plasma triglyceride, cholesterol, and significantly lower adiponectin levels compared with their respective control mice (Figure 1b-d). Other studies have shown that high-fat-diet-induced obesity in mice exhibited lower glucose and insulin tolerance versus normal-diet mice [48]. Similarly, the HFD-fed mice showed a significant decrease in insulin sensitivity, as demonstrated by the GTT and ITT results (Figure 1e,f).…”

Nicotinamide Improves Functional Recovery via Regulation of the RAGE/JNK/NF-κB Signaling Pathway after Brain Injury

“…Injuries to the brain evoked inflammatory responses and the activation of astrocytes and microglia [48,49]. Therefore, in the present study, using western blot analysis, we examined the activation of inflammatory mediators in the ipsilateral side of the treated mice, at day 7.…”

Modulation of Nrf2 by Olive Oil and Wine Polyphenols and Neuroprotection

“…ROS damage cell membranes and increase their rigidity, leading to modifications in proteins, lipids, and cell membrane receptors. With respect to the latter, this alters their function, intracellular signaling, and clustering with other membrane receptors [ 51 ]. Oxidative stress and ROS production can result in cellular damage when constructing the molecular basis, and thus can also result in the progression of a number of neurodegenerative diseases [ 52 , 53 , 54 , 55 , 56 ].…”