PMID: 25731620Mar 4, 2015Paper

Therapeutic approaches to modulating glutathione levels as a pharmacological strategy in Alzheimer's disease

Current Alzheimer Research
N BraidyW Bridge

Abstract

Accumulating evidence has suggested the involvement of oxidative stress in the pathogenesis of Alzheimer's disease (AD). The main endogenous antioxidant, glutathione (GSH), has been shown to decline with ageing and in several age-related degenerative diseases, including AD. Potential options for replenishing GSH levels as a therapeutic target to treat these conditions include the administration of GSH itself, and low toxicity forms of the limiting amino acid for GSH synthesis; cysteine. However, passive GSH uptake is limited due to an unfavourable concentration gradient between the plasma and cytosol. Similarly, cysteine prodrugs have demonstrated limited efficacy to elevate depleted GSH levels in several in vivo and in vitro models of disease. It has been suggested that the decline in GSH levels in AD, may be associated with down regulation of GSH homeostasis rather than substrate limitation. Cellular GSH homeostasis is regulated by non-allosteric feedback inhibition exerted by GSH on glutamate cysteine ligase (GCL), which is responsible for the synthesis of the GSH precursor γ-glutamylcysteine (GGC). In conditions involving down regulated GSH homeostasis, GGC serves as a crucialrate-limiting substrate for GSH synthetase, the ...Continue Reading

Citations

Jan 2, 2016·Biochimica Et Biophysica Acta·Silvia CaioliCristina Zona
Sep 17, 2015·Molecular Neurobiology·Amanda M GleixnerRehana K Leak
Apr 25, 2017·Journal of Proteome Research·Yuanhui MaJohn R Yates
Jun 9, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jianbo ChenYinshi Sun
Nov 9, 2018·Frontiers in Pharmacology·Bee Ling TanHeshu Sulaiman Rahman
Dec 15, 2020·Journal of Dietary Supplements·Peter PressmanRoger Clemens

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.