Sulodexide and Alzheimer’s Disease: A Preliminary Prospective Study

J, Lasierra-Cirujeda; Pascual-Salcedo, María José Aza; Aza-Pascual-Salcedo, Mercedes

doi:10.4236/wjcd.2016.62007

Cited by 4 publications

(2 citation statements)

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“…Some clinical studies about antithrombotic treatments have demonstrated that the inhibition of the PAI-1 produces an endogenous increase of the fibrinolytic activity [254]- [257]. In our experience we have observed that the treatment with sulodexide, an inhibitor of PAI-1 activity, in the prevention of secondary thrombosis in AD in long term produces positive results due to its pharmacological effect [258] [259]. These clinical observations suggest the hypothesis that aging develops a sequence of processes such as obesity, MS, as well as clinical entities such as T2DM and AD, with a common denominator, the increase of the PAI-1.…”

Section: Pai-1 Inhibitionmentioning

confidence: 90%

Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease

J¹,

Pascual-Salcedo²,

Lasierra-Ibañez³

et al. 2016

JBM

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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 (βamyloidosis) 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

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Section: Pai-1 Inhibitionmentioning

confidence: 90%

Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease

J¹,

Pascual-Salcedo²,

Lasierra-Ibañez³

et al. 2016

JBM

Self Cite

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“…Besides, it is of great interest the pathophysiological function developed by PAI-1 in aging and the multiple pathology associated: obesity, metabolic syndrome, type 2 diabetes, neurodegenerative pathology (mainly in Alzheimer's Disease and Parkinson's Disease), cancer (PAI-1 can be involved in the onset, progression and metastasis of some neoplasia), cardiovascular processes and thromboembolic complications. These clinical entities clearly show increased levels of PAI-1, leading some researchers to suggest the use of PAI-1 inhibitors with therapeutic purposes in those risk processes where reduction to physiological levels could be of interest [32][33][34][35][36][37][38][39].…”

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confidence: 99%