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

2019 ◽  
Vol 25 (40) ◽  
pp. 5578-5587 ◽  
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.

scholarly journals New Insights in the Amyloid-Beta Interaction with Mitochondria

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Carlos Spuch ◽  
Saida Ortolano ◽  
Carmen Navarro
Keyword(s):  
Alzheimer’S Disease ◽  
Reactive Oxygen Species ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Amyloid Beta ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Mitochondrial Proteins ◽  
Oxygen Species ◽  
Species Production

Biochemical and morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer’s disease (AD). Particularly, mitochondrial dysfunction is a hallmark of amyloid-beta-induced neuronal toxicity in Alzheimer’s disease. The recent emphasis on the intracellular biology of amyloid-beta and its precursor protein (APP) has led researchers to consider the possibility that mitochondria-associated and mitochondrial amyloid-beta may directly cause neurotoxicity. Both proteins are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron transport chain, increase reactive oxygen species production, cause mitochondrial damage, and prevent neurons from functioning normally. In this paper, we will outline current knowledge of the intracellular localization of amyloid-beta. Moreover, we summarize evidence from AD postmortem brain as well as animal AD models showing that amyloid-beta triggers mitochondrial dysfunction through a number of pathways such as impairment of oxidative phosphorylation, elevation of reactive oxygen species production, alteration of mitochondrial dynamics, and interaction with mitochondrial proteins. Thus, this paper supports the Alzheimer cascade mitochondrial hypothesis such as the most important early events in this disease, and probably one of the future strategies on the therapy of this neurodegenerative disease.

scholarly journals Towards a Consensus on Alzheimer’s Disease Comorbidity?

2021 ◽  
Vol 10 (19) ◽  
pp. 4360
Author(s):  
Iska Avitan ◽  
Yudit Halperin ◽  
Trishna Saha ◽  
Naamah Bloch ◽  
Dana Atrahimovich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Potential Role ◽  
Oxygen Species ◽  
Degenerative Diseases ◽  
Comorbid Diseases

Alzheimer’s disease (AD) is often comorbid with other pathologies. First, we review shortly the diseases most associated with AD in the clinic. Then we query PubMed citations for the co-occurrence of AD with other diseases, using a list of 400 common pathologies. Significantly, AD is found to be associated with schizophrenia and psychosis, sleep insomnia and apnea, type 2 diabetes, atherosclerosis, hypertension, cardiovascular diseases, obesity, fibrillation, osteoporosis, arthritis, glaucoma, metabolic syndrome, pain, herpes, HIV, alcoholism, heart failure, migraine, pneumonia, dyslipidemia, COPD and asthma, hearing loss, and tobacco smoking. Trivially, AD is also found to be associated with several neurodegenerative diseases, which are disregarded. Notably, our predicted results are consistent with the previously published clinical data and correlate nicely with individual publications. Our results emphasize risk factors and promulgate diseases often associated with AD. Interestingly, the comorbid diseases are often degenerative diseases exacerbated by reactive oxygen species, thus underlining the potential role of antioxidants in the treatment of AD and comorbid diseases.

scholarly journals Influence of Acetylcholinesterase Inhibitors Used in Alzheimer’s Disease Treatment on the Activity of Antioxidant Enzymes and the Concentration of Glutathione in THP-1 Macrophages under Fluoride-Induced Oxidative Stress

2018 ◽  
Vol 16 (1) ◽  
pp. 10 ◽  
Author(s):  
Marta Goschorska ◽  
Izabela Gutowska ◽  
Irena Baranowska-Bosiacka ◽  
Katarzyna Piotrowska ◽  
Emilia Metryka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Reactive Oxygen Species ◽  
Alzheimer's Disease ◽  
Antioxidant Enzymes ◽  
Antioxidant Properties ◽  
Reactive Oxygen ◽  
Acetylcholinesterase Inhibitors ◽  
Oxygen Species ◽  
Ache Inhibitors

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.

scholarly journals A central role for ROS in the functional remodelling of L-type Ca 2+ channels by hypoxia

2005 ◽  
Vol 360 (1464) ◽  
pp. 2247-2254 ◽  
Author(s):  
Chris Peers ◽  
Jason L Scragg ◽  
John P Boyle ◽  
Ian M Fearon ◽  
Shafeena C Taylor ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Reactive Oxygen Species ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Cellular Systems ◽  
Oxygen Species ◽  
Excitable Cells ◽  
Amyloid Peptides ◽  
Channel Trafficking ◽  
Cellular Basis

Periods of prolonged hypoxia are associated clinically with an increased incidence of dementia, the most common form of which is Alzheimer's disease. Here, we review recent studies aimed at providing a cellular basis for this association. Hypoxia promoted an enhanced secretory response of excitable cells via formation of a novel Ca 2+ influx pathway associated with the formation of amyloid peptides of Alzheimer's disease. More strikingly, hypoxia potentiated Ca 2+ influx specifically through L-type Ca 2+ channels in three distinct cellular systems. This effect was post-transcriptional, and evidence suggests it occurred via increased formation of amyloid peptides which alter Ca 2+ channel trafficking via a mechanism involving increased production of reactive oxygen species by mitochondria. This action of hypoxia is likely to contribute to dysregulation of Ca 2+ homeostasis, which has been proposed as a mechanism of cell death in Alzheimer's disease. We suggest, therefore, that our data provide a cellular basis to account for the known increased incidence of Alzheimer's disease in patients who have suffered prolonged hypoxic episodes.

scholarly journals Generation of reactive oxygen species and activation of NF-κB by non-Aβ component of Alzheimer's disease amyloid

2002 ◽  
Vol 82 (2) ◽  
pp. 305-315 ◽  
Author(s):  
Seigo Tanaka ◽  
Masanori Takehashi ◽  
Naomi Matoh ◽  
Shinya Iida ◽  
Tomoki Suzuki ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Reactive Oxygen Species ◽  
Alzheimer's Disease ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Amyloid β oligomers constrict human capillaries in Alzheimer’s disease via signaling to pericytes

Science ◽  
2019 ◽  
Vol 365 (6450) ◽  
pp. eaav9518 ◽  
Author(s):  
Ross Nortley ◽  
Nils Korte ◽  
Pablo Izquierdo ◽  
Chanawee Hirunpattarasilp ◽  
Anusha Mishra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Reactive Oxygen Species ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Oxygen Species ◽  
Brain Capillaries ◽  
Disease Relevance ◽  
The Brain ◽  
Capillary Walls

Cerebral blood flow is reduced early in the onset of Alzheimer’s disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. We used live and rapidly fixed biopsied human tissue to establish disease relevance, and rodent experiments to define mechanism. We found that in humans with cognitive decline, amyloid β (Aβ) constricts brain capillaries at pericyte locations. This was caused by Aβ generating reactive oxygen species, which evoked the release of endothelin-1 (ET) that activated pericyte ETA receptors. Capillary, but not arteriole, constriction also occurred in vivo in a mouse model of AD. Thus, inhibiting the capillary constriction caused by Aβ could potentially reduce energy lack and neurodegeneration in AD.

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