Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease
Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease作者机构：Centro Médico Hematológico Logrono Spain Pharmaceutical Act Ministry of Health La Rioja Regional Government Logrono Spain Aragon Health Service Zaragoza Spain
出 版 物：《Journal of Biosciences and Medicines》 (生物科学与医学（英文）)
年 卷 期：2016年第4卷第5期
页 面：1-20页
主 题：Aging Alzheimer’s Disease T2DM PAI-1 Glutathione
摘 要：Aging can be interpreted as an unavoidable process whose end point is the death. Aging entails, in the hemostasis field, some changes that favour blood hypercoagulability. Both the plasminogen activator inhibitor (PAI-1), specific inhibitor of the tissue plasminogen activator (t-PA), accompanied by the oxidative stress and the marked decrease of the main antioxidant—glutathione are fundamental in the bases of elderly pathologies which can cause death. There is some scientific evidence of the relationship between aging, neuro-degenerative diseases, an excessive production of reactive oxygen species and the decrease of proteolysis in brain. The cerebral plasminogen/plasmin system represents the essential proteolytic mechanism that degrades amyloid peptides (β-amyloidosis) for action of plasmin with effectiveness. This physiologic process is being considered as a preventive neurodegenerative mechanism. At the same time, the decrease of glutathione levels in aging entails a decrease of cerebral plasmin activity and a progressive descent of t-PA activity due to a descent in t-PA expression and an increase in PAI production. All of them entail an increment of amyloid beta peptides (Aβ) production and a lower level of their clearance. Both mechanisms, oxidative stress, direct consequence of the oxygenate metabolism of aerobics cells, and changes in the systemic fibrinolysis and cerebral b-amyloidolytic activity, play a very important role in thromboembolic disease, metabolic syndrome—obesity, insulin resistance, hyperglycemia—, type 2 Diabetes Mellitus and Alzheimer’s disease, clinical processes that accompany the aging. In this revision we show the importance of the interaction between glutathione, proteolytic t-PA/plasminogen/plasmin system, and the inhibitor PAI-1 in aging physiopathology, whose results suggest the hypothesis of the importance of a therapeutic strategy using the inhibition of PAI-1 as a goal, because it is increased in the different aging pathologic processes.
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