Antioxidant approaches for the treatment of Alzheimer’s disease

Abstract

Oxidative stress is an important factor, and one that acts in the earliest stages, of Alzheimer's disease (AD) pathogenesis. The reduction of oxidative stress has been tested as a therapy for AD. While the trial of vitamin E supplementation in moderately severe AD is the most promising so far, it also reveals the limitations of general antioxidant therapies that simply lower oxidative stress and, therefore, the complexity of the redox system. The multiple contributing factors that foster the clinical manifestations of AD should be considered when designing antioxidative stress therapy. In this article, we discuss the multiple pathogenic mechanisms of oxidative stress in AD and the potential targeting approaches.

Targeting NOX enzymes in the central nervous system: therapeutic opportunities

“…Of particular note, parallel administration of N-acetyl cysteine could also moderately diminish negative symptoms, such as akathisia [16]. However, as for cardiovascular diseases, the use of antioxidant therapies has led to contradictory and mostly disappointing outcomes in clinical trials for CNS diseases [82], in spite of promising results obtained in in vitro studies and in animal models for AD [141], and other neuropathologies, such as stroke [134] or ALS [10]. Failure of antioxidant treatments should not necessarily preclude the search of therapies targeting oxidative stress to treat neuropathologies because there are numerous possible reasons for the apparent failure of antioxidant therapies, including lack of specificity, potency, and bioavailability of antioxidant drugs, poor trial design, or lack of relevant biomarkers of oxidation.…”

The Amyloid Precursor Protein (APP) Family Members are Key Players in S-adenosylmethionine Formation by MAT2A and Modify BACE1 and PSEN1 Gene Expression-Relevance for Alzheimer's Disease

“…Lipid membranes belong to the most vulnerable cellular components to oxidative stress, and membranes in susceptible regions of the brain are compositionally distinct from membranes in other tissues (45). Similarly, antioxidant therapies lowering oxidative stress in AD pathogenesis are under discussion (47).…”

Involvement and interplay of Parkin, PINK1, and DJ1 in neurodegenerative and neuroinflammatory disorders

“…There is ample literature supporting the involvement of mitochondrial dysfunction [18] and oxidative stress [146] in the pathogenesis of AD. Since it has been proposed that DJ-1 has antioxidant properties and modulates mitochondrial integrity and function it remains remarkable that there are only a few reports that have addressed the link between AD and DJ-1.…”