Back to Browse Journals » Journal of Blood Medicine » Volume 4

Beta-amyloidolysis and glutathione in Alzheimer's disease

Authors Lasierra-Cirujeda J, Coronel P, Aza MJ, Gimeno M

Published Date April 2013 Volume 2013:4 Pages 31—38

DOI http://dx.doi.org/10.2147/JBM.S35496

Received 29 June 2012, Accepted 4 December 2012, Published 15 April 2013

J Lasierra-Cirujeda,1 P Coronel,2 MJ Aza,3 M Gimeno2

1CM Hematológico SC, Logroño, La Rioja, Spain; 2Tedec-Meiji Farma, SA, Alcalá de Henares, Madrid, Spain; 3Pharmaceutical Act, Ministry of Health, Regional Government, La Rioja, Spain

Abstract: In this review, we hypothesized the importance of the interaction between the brain glutathione (GSH) system, the proteolytic tissue plasminogen activator (t-PA)/plasminogen/plasmin system, regulated by plasminogen activator inhibitor (PAI-1), and neuroserpin in the pathogenesis of Alzheimer's disease. The histopathological characteristic hallmark that gives personality to the diagnosis of Alzheimer's disease is the accumulation of neurofibroid tangles located intracellularly in the brain, such as the protein tau and extracellular senile plaques made primarily of amyloidal substance. These formations of complex etiology are intimately related to GSH, brain protective antioxidants, and the proteolytic system, in which t-PA plays a key role. There is scientific evidence that suggests a relationship between aging, a number of neurodegenerative disorders, and the excessive production of reactive oxygen species and accompanying decreased brain proteolysis. The plasminogen system in the brain is an essential proteolytic mechanism that effectively degrades amyloid peptides ("beta-amyloidolysis") through action of the plasmin, and this physiologic process may be considered to be a means of prevention of neurodegenerative disorders. In parallel to the decrease in GSH levels seen in aging, there is also a decrease in plasmin brain activity and a progressive decrease of t-PA activity, caused by a decrease in the expression of the t-PA together with an increase of the PAI-1 levels, which rise to an increment in the production of amyloid peptides and a lesser clearance of them. Better knowledge of the GSH mechanism and cerebral proteolysis will allow us to hypothesize about therapeutic practices.

Keywords: glutathione, Alzheimer's disease, t-PA, PAI-1, plasminogen

Download Article [PDF] View Full Text [HTML] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Readers of this article also read:

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Glaucoma associated with the management of rhegmatogenous retinal detachment

Mangouritsas G, Mourtzoukos S, Portaliou DM, Georgopoulos VI, Dimopoulou A, Feretis E

Clinical Ophthalmology 2013, 7:727-734

Published Date: 15 April 2013

In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

Lim SCB, Paech MJ, Sunderland B, Liu Y

Drug Design, Development and Therapy 2013, 7:317-324

Published Date: 12 April 2013

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

The amorphous solid dispersion of the poorly soluble ABT-102 forms nano/microparticulate structures in aqueous medium: impact on solubility

Frank KJ, Westedt U, Rosenblatt KM, Hölig P, Rosenberg J, Mägerlein M, Fricker G, Brandl M

International Journal of Nanomedicine 2012, 7:5757-5768

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Heart detection and diagnosis based on ECG and EPCG relationships

Phanphaisarn W, Roeksabutr A, Wardkein P, Koseeyaporn J, Yupapin PP

Medical Devices: Evidence and Research 2011, 4:133-144

Published Date: 26 August 2011

Corrigendum: Softec HD hydrophilic acrylic intraocular lens: biocompatibility and precision

Espandar L, Sikder S, Moshirfar M

Clinical Ophthalmology 2011, 5:159-160

Published Date: 6 February 2011

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010