Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During inflammation, several cell types synthesize and secrete phospholipase A2 that catalyses lipid oxidation in LDL. Myeloperoxidase, a haeme protein secreted by activated phagocytes, oxidizes L-tyrosine to a tyrosyl radical that is a physiological catalyst for the initiation of lipid oxidation in LDL. Lipid oxidation results in the generation of aldehydes that substitute lysine residues in the apolipoprotein B-100 moiety. Lipid together with protein oxidation in LDL results in the generation of oxidized LDL. We, among others, have demonstrated an association between coronary heart disease (CHD) and increased plasma levels of oxidized LDL. Recently, we have demonstrated a higher prevalence of elevated oxidized LDL in persons with high-calculated CHD risk prior to events. The odds of having elevated oxidized LDL for persons with high-calculated CHD risk prior to events were even higher than for persons with diagnosed CHD. A likely explanation is that once CHD has been diagnosed the patients are more treated with a statin that appears to decrease oxidized LDL even beyond its cholesterol-lowering effect. We have identified several metabolic syndrome components (high triglycerides, low HDL-cholesterol, glucose intolerance and diabetes) that independently of LDL-cholesterol, predicted high levels of oxidized LDL. Finally, elevated oxidized LDL predicted myocardial infarction in the Health ABC cohort consisting of well-functioning elderly people, even after adjusting for age, gender, race, smoking, and the metabolic syndrome.
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PMID:Oxidized LDL and coronary heart disease. 1552 50

Metabolic syndrome (MetS) is a cluster of risk factors that lead to microvascular dysfunction and chronic cerebral hypoperfusion (CCH). Long-standing reduction in oxygen and energy supply leads to brain hypoxia and protein misfolding, thereby linking CCH to Alzheimer's disease. Protein misfolding results in neurodegeneration as revealed by studying different experimental models of CCH. Regulating proteostasis network through pathways like the unfolded protein response (UPR), the ubiquitin-proteasome system (UPS), chaperone-mediated autophagy (CMA), and macroautophagy emerges as a novel target for neuroprotection. Lipoxin A4 methyl ester, baclofen, URB597, N-stearoyl-L-tyrosine, and melatonin may pose potential neuroprotective agents for rebalancing the proteostasis network under CCH. Autophagy is one of the most studied pathways of proteostatic cell response against the decrease in blood supply to the brain though the role of the UPR-specific chaperones and the UPS system in CCH deserves further research. Pharmacotherapy targeting misfolded proteins at different stages in the proteostatic pathway might be promising in treating cognitive impairment following CCH.
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PMID:Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome. 2990 35