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

Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland
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Academic Editor: Jane Grant-Kels
J. Clin. Med. 2017, 6(5), 55; https://doi.org/10.3390/jcm6050055
Received: 29 November 2016 / Revised: 6 May 2017 / Accepted: 18 May 2017 / Published: 21 May 2017
(This article belongs to the Special Issue The Role of Oxidant Stress in Disease)
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. View Full-Text
Keywords: interleukin-18; inflammation; oxidative stress; Alzheimer’s disease; metabolic syndrome; blood-brain barrier; BVR; DJ-1; DDAH; peroxiredoxin; enolase; 14-3-3; MMP14; Bcl-xL interleukin-18; inflammation; oxidative stress; Alzheimer’s disease; metabolic syndrome; blood-brain barrier; BVR; DJ-1; DDAH; peroxiredoxin; enolase; 14-3-3; MMP14; Bcl-xL
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Ojala, J.O.; Sutinen, E.M. The Role of Interleukin-18, Oxidative Stress and Metabolic Syndrome in Alzheimer’s Disease. J. Clin. Med. 2017, 6, 55.

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