Role of Oxidative Stress and Metal Toxicity in the Progression of Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the life-threatening neurodegenerative disorders in the elderly (>60 years) and incurable across the globe to date. AD is caused by the involvement of various genetic, environmental and lifestyle factors that affect neuronal cells to degenerate over the period of time. The oxidative stress is engaged in the pathogenesis of various disorders and its key role is also linked to the etiology of AD. AD is attributed by neuronal loss, abnormal accumulation of Amyloid-β (Aβ) and neurofibrillary tangles (NFTs) with severe memory impairments and other cognitive dysfunctions which lead to the loss of synapses and neuronal death and eventual demise of the individual. Increased production of reactive oxygen species (ROS), loss of mitochondrial function, altered metal homeostasis, aberrant accumulation of senile plaque and mitigated antioxidant defense mechanism all are indulged in the progression of AD. In spite of recent advances in biomedical research, the underlying mechanism of disruption of redox balance and the actual source of oxidative stress is still obscure. This review highlights the generation of ROS through different mechanisms, the role of some important metals in the progression of AD and free radical scavenging by endogenous molecule and supplementation of nutrients in AD.

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Potential Role of Phenolic Extracts of Mentha in Managing Oxidative Stress and Alzheimer’s Disease

Antioxidants ◽

10.3390/antiox9070631 ◽

2020 ◽

Vol 9 (7) ◽

pp. 631

Author(s):

Doaa M. Hanafy ◽

Geoffrey E. Burrows ◽

Paul D. Prenzler ◽

Rodney A. Hill

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Potential Role ◽

The Elderly ◽

Future Research ◽

Phenolic Constituents ◽

The Central Nervous System ◽

Developed Nations

With an increase in the longevity and thus the proportion of the elderly, especially in developed nations, there is a rise in pathological conditions that accompany ageing, such as neurodegenerative disorders. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive and memory decline. The pathophysiology of the disease is poorly understood, with several factors contributing to its development, such as oxidative stress, neuroinflammation, cholinergic neuronal apoptotic death, and the accumulation of abnormal proteins in the brain. Current medications are only palliative and cannot stop or reverse the progression of the disease. Recent clinical trials of synthetic compounds for the treatment of AD have failed because of their adverse effects or lack of efficacy. Thus, there is impetus behind the search for drugs from natural origins, in addition to the discovery of novel, conventional therapeutics. Mints have been used traditionally for conditions relevant to the central nervous system. Recent studies showed that mint extracts and/or their phenolic constituents have a neuroprotective potential and can target multiple events of AD. In this review, we provide evidence of the potential role of mint extracts and their derivatives as possible sources of treatments in managing AD. Some of the molecular pathways implicated in the development of AD are reviewed, with focus on apoptosis and some redox pathways, pointing to mechanisms that may be modulated for the treatment of AD, and the need for future research invoking knowledge of these pathways is highlighted.

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Oxidative Stress and the Pathogenesis of Alzheimer's Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/316523 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 248

Author(s):

Yan Zhao ◽

Baolu Zhao

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Senile Plaques ◽

Neuronal Loss ◽

The Elderly ◽

Redox Balance ◽

Tau Proteins ◽

Molecular Events ◽

Abnormal Accumulation

Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia in the elderly. Patients with AD suffer a gradual deterioration of memory and other cognitive functions, which eventually leads to a complete incapacity and death. A complicated array of molecular events has been implicated in the pathogenesis of AD. The major pathological characteristics of AD brains are the presence of senile plaques, neurofibrillary tangles, and neuronal loss. Growing evidence has demonstrated that oxidative stress is an important factor contributing to the initiation and progression of AD. However, the mechanisms that lead to the disruption of redox balance and the sources of free radicals remain elusive. The excessive reactive oxygen species may be generated from mechanisms such as mitochondria dysfunction and/or aberrant accumulation of transition metals, while the abnormal accumulation of Abeta and tau proteins appears to promote the redox imbalance. The resulted oxidative stress has been implicated in Abeta- or tau-induced neurotoxicity. In addition, evidence has suggested that oxidative stress may augment the production and aggregation of Abeta and facilitate the phosphorylation and polymerization of tau, thus forming a vicious cycle that promotes the initiation and progression of AD.

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Faculty Opinions recommendation of Role Of Oxidative Stress And Metal Toxicity In The Progression Of Alzheimer's Disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737455971.793571903 ◽

2020 ◽

Author(s):

Pravat K Mandal

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Metal Toxicity

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Isovitexin modulates autophagy in Alzheimer’s disease via miR-107 signalling

Translational Neuroscience ◽

10.1515/tnsci-2020-0109 ◽

2020 ◽

Vol 11 (1) ◽

pp. 391-401

Author(s):

Jiang Cheng ◽

Guowei Wang ◽

Na Zhang ◽

Fang Li ◽

Lina Shi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Memory Loss ◽

The Elderly ◽

Tnf Α ◽

Autophagic Process ◽

Molecular Signals ◽

Ad Mouse Model ◽

Mtor Signalling

AbstractBackground:Alzheimer’s disease (AD) is an ultimately fatal, degenerative brain disease in the elderly people. In the current work, we assessed the defensive capability of isovitexin (IVX) through an intracerebroventricular injection of streptozotocin (STZ)-induced AD mouse model.Methods:Mice were separated into four cohorts: sham-operated control mice; STZ-intoxicated Alzheimer’s mice; IVX cohort, IVX + STZ; and Ant-107 cohort, antagomiR-107 + IVX/STZ as in the IVX cohort.Results:The outcomes indicated that IVX administration ameliorated spatial memory loss and blunted a cascade of neuro-noxious episodes – including increased amyloid-beta (Aβ) and degraded myelin basic protein burden, neuroinflammation (represented by elevated caspase-1, TNF-α and IL-6 levels) and autophagic dysfunction (represented by altered LC3-II, Atg7 and beclin-1 expressions) – via the inhibition of PI3K/Akt/mTOR signalling axis. We considered the question of whether the epigenetic role of microRNA-107 (miR-107) has any impact on these events, by using antagomiR-107.Conclusion:This probing underscored that miR-107 could be a pivotal regulatory button in the activation of molecular signals linked with the beneficial autophagic process and anti-inflammatory activities in relation to IVX treatment. Hence, this report exemplifies that IVX could guard against Aβ toxicity and serve as an effectual treatment for patients afflicted with AD.

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Astrocytes and Adenosine A2A Receptors: Active Players in Alzheimer’s Disease

Frontiers in Neuroscience ◽

10.3389/fnins.2021.666710 ◽

2021 ◽

Vol 15 ◽

Author(s):

Cátia R. Lopes ◽

Rodrigo A. Cunha ◽

Paula Agostinho

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Β ◽

The Elderly ◽

Synaptic Function ◽

Morphological Alterations ◽

Functional Changes ◽

A2a Receptors ◽

Novel Therapeutic Strategies

Astrocytes, through their numerous processes, establish a bidirectional communication with neurons that is crucial to regulate synaptic plasticity, the purported neurophysiological basis of memory. This evidence contributed to change the classic “neurocentric” view of Alzheimer’s disease (AD), being astrocytes increasingly considered a key player in this neurodegenerative disease. AD, the most common form of dementia in the elderly, is characterized by a deterioration of memory and of other cognitive functions. Although, early cognitive deficits have been associated with synaptic loss and dysfunction caused by amyloid-β peptides (Aβ), accumulating evidences support a role of astrocytes in AD. Astrocyte atrophy and reactivity occurring at early and later stages of AD, respectively, involve morphological alterations that translate into functional changes. However, the main signals responsible for astrocytic alterations in AD and their impact on synaptic function remain to be defined. One possible candidate is adenosine, which can be formed upon extracellular catabolism of ATP released by astrocytes. Adenosine can act as a homeostatic modulator and also as a neuromodulator at the synaptic level, through the activation of adenosine receptors, mainly of A1R and A2AR subtypes. These receptors are also present in astrocytes, being particularly relevant in pathological conditions, to control the morphofunctional responses of astrocytes. Here, we will focus on the role of A2AR, since they are particularly associated with neurodegeneration and also with memory processes. Furthermore, A2AR levels are increased in the AD brain, namely in astrocytes where they can control key astrocytic functions. Thus, unveiling the role of A2AR in astrocytes function might shed light on novel therapeutic strategies for AD.

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Modulating Effect of Diet on Alzheimer’s Disease

Diseases ◽

10.3390/diseases7010012 ◽

2019 ◽

Vol 7 (1) ◽

pp. 12 ◽

Cited By ~ 6

Author(s):

Paloma Fernández-Sanz ◽

Daniel Ruiz-Gabarre ◽

Vega García-Escudero

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Inflammatory Response ◽

Scientific Evidence ◽

Senile Plaques ◽

Neuronal Loss ◽

Pleiotropic Effect ◽

Amyloid Peptide ◽

Dietary Recommendations

As life expectancy is growing, neurodegenerative disorders, such as Alzheimer’s disease, are increasing. This disease is characterised by the accumulation of intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein, senile plaques composed of an extracellular deposit of β-amyloid peptide (Aβ), and neuronal loss. This is accompanied by deficient mitochondrial function, increased oxidative stress, altered inflammatory response, and autophagy process impairment. The present study gathers scientific evidence that demonstrates that specific nutrients exert a direct effect on both Aβ production and Tau processing and their elimination by autophagy activation. Likewise, certain nutrients can modulate the inflammatory response and the oxidative stress related to the disease. However, the extent to which these effects come with beneficial clinical outcomes remains unclear. Even so, several studies have shown the benefits of the Mediterranean diet on Alzheimer’s disease, due to its richness in many of these compounds, to which can be attributed their neuroprotective properties due to the pleiotropic effect they show on the aforementioned processes. These indications highlight the potential role of adequate dietary recommendations for clinical management of both Alzheimer’s diagnosed patients and those in risk of developing it, emphasising once again the importance of diet on health.

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Future Therapeutic Perspectives into the Alzheimer’s Disease Targeting the Oxidative Stress Hypothesis

Molecules ◽

10.3390/molecules24234410 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4410 ◽

Cited By ~ 10

Author(s):

Jéssika P. Teixeira ◽

Alexandre A. de Castro ◽

Flávia V. Soares ◽

Elaine F. F. da Cunha ◽

Teodorico C. Ramalho

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neuronal Cell ◽

The Elderly ◽

Oxygen Species ◽

Chain Reaction ◽

Radical Chain ◽

App Metabolism ◽

Radical Chain Reaction

Alzheimer’s disease (AD) is a neurodegenerative disease that is usually accompanied by aging, increasingly being the most common cause of dementia in the elderly. This disorder is characterized by the accumulation of beta amyloid plaques (Aβ) resulting from impaired amyloid precursor protein (APP) metabolism, together with the formation of neurofibrillary tangles and tau protein hyperphosphorylation. The exacerbated production of reactive oxygen species (ROS) triggers the process called oxidative stress, which increases neuronal cell abnormalities, most often followed by apoptosis, leading to cognitive dysfunction and dementia. In this context, the development of new therapies for the AD treatment is necessary. Antioxidants, for instance, are promising species for prevention and treatment because they are capable of disrupting the radical chain reaction, reducing the production of ROS. These species have also proven to be adjunctive to conventional treatments making them more effective. In this sense, several recently published works have focused their attention on oxidative stress and antioxidant species. Therefore, this review seeks to show the most relevant findings of these studies.

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Investigating the role of neuronal oxidative stress in early Alzheimer’s disease pathology

Alzheimer s & Dementia ◽

10.1002/alz.041171 ◽

2020 ◽

Vol 16 (S3) ◽

Author(s):

Morgan K. Foret ◽

Sonia Do Carmo ◽

Lindsay A. Welikovitch ◽

Chiara Orciani ◽

A. Claudio Cuello

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Alzheimer’S Disease

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The Role of APP O-Glycosylation in Alzheimer’s Disease

Biomolecules ◽

10.3390/biom10111569 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1569

Author(s):

Keiko Akasaka-Manya ◽

Hiroshi Manya

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Senile Plaque ◽

Amyloid Β ◽

Pathological Feature ◽

People With Dementia ◽

New Findings ◽

Neurodegenerative Dementia ◽

Aβ Production

The number of people with dementia is increasing rapidly due to the increase in the aging population. Alzheimer’s disease (AD) is a type of neurodegenerative dementia caused by the accumulation of abnormal proteins. Genetic mutations, smoking, and several other factors have been reported as causes of AD, but alterations in glycans have recently been demonstrated to play a role in AD. Amyloid-β (Aβ), a cleaved fragment of APP, is the source of senile plaque, a pathological feature of AD. APP has been reported to undergo N- and O-glycosylation, and several Polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) have been shown to have catalytic activity for the transfer of GalNAc to APP. Since O-glycosylation in the proximity of a cleavage site in many proteins has been reported to be involved in protein processing, O-glycans may affect the cleavage of APP during the Aβ production process. In this report, we describe new findings on the O-glycosylation of APP and Aβ production.

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