Apolipoprotein D in Oxidative Stress and Inflammation

Abstract

Apolipoprotein D (ApoD) is lipocalin able to bind hydrophobic ligands. The APOD gene is upregulated in a number of pathologies, including Alzheimer’s disease, Parkinson’s disease, cancer, and hypothyroidism. Upregulation of ApoD is linked to decreased oxidative stress and inflammation in several models, including humans, mice, Drosophila melanogaster and plants. Studies suggest that the mechanism through which ApoD modulates oxidative stress and regulate inflammation is via its capacity to bind arachidonic acid (ARA). This polyunsaturated omega-6 fatty acid can be metabolised to generate large variety of pro-inflammatory mediators. ApoD serves as a sequester, blocking and/or altering arachidonic metabolism. In recent studies of diet-induced obesity, ApoD has been shown to modulate lipid mediators derived from ARA, but also from eicosapentaenoic acid and docosahexaenoic acid in an anti-inflammatory way. High levels of ApoD have also been linked to better metabolic health and inflammatory state in the round ligament of morbidly obese women. Since ApoD expression is upregulated in numerous diseases, it might serve as a therapeutic agent against pathologies aggravated by OS and inflammation such as many obesity comorbidities. This review will present the most recent findings underlying the central role of ApoD in the modulation of both OS and inflammation.

Plasma Concentrations of High Mobility Group Box 1 Proteins and Soluble Receptors for Advanced Glycation End-Products Are Relevant Biomarkers of Cognitive Impairment in Alcohol Use Disorder: A Pilot Study

“…Interestingly, elevated ROS/RNS levels were negatively correlated with the onset of alcohol consumption, suggesting that AUD patients starting alcohol consumption at early ages may have higher oxidative damage that contributes to neuronal cell death [ 44 ]. In addition, ApoD was positively correlated with duration of alcohol abstinence, suggesting a glial cell-associated regenerative function and reduced sensitivity to oxidative stress following alcohol-induced brain damage [ 45 , 46 ]. To identify reliable biomarkers of alcohol-induced neurocognitive disorder, a binary logistic regression analysis was performed to predict CI in AUD patients.…”

“…Our results indicated higher plasma ApoD concentrations in AUD patients, similar to those of AD patients, and in AUD patients with cognitive impairment, similar to those of AD patients with cognitive impairment. Moreover, plasma ApoD concentrations were positively correlated with the duration of alcohol abstinence, suggesting a function of neuronal preservation and protection in response to decreasing oxidative stress and inflammation during alcohol withdrawal [ 45 , 46 ]. Nevertheless, further research is necessary to better understand the underlying mechanism of oxidative stress activated by alcohol that associate ApoD with cognitive impairment.…”

The potential protective role of Parkinson’s disease against hypothyroidism: co-localisation and bidirectional Mendelian randomization study

“…PD and hypothyroidism share similar pathogenic mechanisms, such as oxidative stress and inflammation. Studies have shown that apo D expression is upregulated in both diseases, and its antioxidant and anti-inflammatory effects provide an interesting avenue for further research ( Fyfe-Desmarais et al, 2023 ). The mechanisms by which PD reduces the risk of hypothyroidism are unknown.…”

Plasma Proteomics-Based Discovery of Mechanistic Biomarkers of Hyperbaric Stress and Pulmonary Oxygen Toxicity

“…The singular protein uniquely expressed in O 2 vs. EAN at POST, APOD, is one of many apolipoproteins secreted and expressed in many tissues including respiratory epithelial cells (i.e., bronchus); it is a multi-ligand protein that supports many functions including those in oxidative stress and inflammation [ 24 ]. APOD has been well-studied [ 25 ] as an antioxidant with known structural mechanisms. The fact that APOD was uniquely expressed O 2 POST vs. EAN may reflect a difference in the nature of stress experienced in each condition.…”