Discussion of the Role of the Extracellular Signal-Regulated Kinase-Phospholipase A2Pathway in Production of Reactive Oxygen Species in Alzheimer's Disease

It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer’s disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is involved in AD pathogenesis, in our study we attempted to examine the influence of donepezil and rivastigmine on the activity of antioxidant enzymes and glutathione concentration in macrophages—an important source of reactive oxygen species and crucial for oxidative stress progression. The macrophages were exposed to sodium fluoride induced oxidative stress. The antioxidant enzymes activity and concentration of glutathione were measured spectrophotometrically. The generation of reactive oxygen species was visualized by confocal microscopy. The results of our study showed that donepezil and rivastigmine had a stimulating effect on catalase activity. However, when exposed to fluoride-induced oxidative stress, the drugs reduced the activity of some antioxidant enzymes (Cat, SOD, GR). These observations suggest that the fluoride-induced oxidative stress may suppress the antioxidant action of AChE inhibitors. Our results may have significance in the clinical practice of treatment of AD and other dementia diseases.

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γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-10-0277 ◽

2010 ◽

Vol 9 (8) ◽

pp. 2196-2207 ◽

Cited By ~ 49

Author(s):

Ramaswamy Kannappan ◽

Jayaraj Ravindran ◽

Sahdeo Prasad ◽

Bokyung Sung ◽

Vivek R. Yadav ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Death Receptors ◽

Oxygen Species ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Induced Apoptosis

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The Role of Mitochondrial Dysfunction in the Progression of Alzheimer’s Disease

Current Medicinal Chemistry ◽

10.2174/0929867324666170616110111 ◽

2019 ◽

Vol 25 (40) ◽

pp. 5578-5587 ◽

Cited By ~ 16

Author(s):

Claus Desler ◽

Meryl S. Lillenes ◽

Tone Tønjum ◽

Lene Juel Rasmussen

Keyword(s):

Alzheimer’S Disease ◽

Reactive Oxygen Species ◽

Alzheimer's Disease ◽

Mitochondrial Dysfunction ◽

De Novo ◽

Oxygen Species ◽

De Novo Synthesis ◽

Atp Production ◽

Essential Phospholipids

The current molecular understanding of Alzheimer’s disease (AD) has still not resulted in successful interventions. Mitochondrial dysfunction of the AD brain is currently emerging as a hallmark of this disease. One mitochondrial function often affected in AD is oxidative phosphorylation responsible for ATP production, but also for production of reactive oxygen species (ROS) and for the de novo synthesis of pyrimidines. This paper reviews the role of mitochondrial produced ROS and pyrimidines in the aetiology of AD and their proposed role in oxidative degeneration of macromolecules, synthesis of essential phospholipids and maintenance of mitochondrial viability in the AD brain.

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