scholarly journals Oxidative Stress and Metabolic Syndrome: Cause or Consequence of Alzheimer's Disease?

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Diana Luque-Contreras ◽  
Karla Carvajal ◽  
Danira Toral-Rios ◽  
Diana Franco-Bocanegra ◽  
Victoria Campos-Peña
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metabolic Syndrome ◽  
Neuronal Damage ◽  
Critical Role ◽  
Neurofibrillary Tangle ◽  
The Elderly ◽  
Amyloid A ◽  
New Therapeutic Approaches

Alzheimer’s disease (AD) is a major neurodegenerative disease affecting the elderly. Clinically, it is characterized by a progressive loss of memory and cognitive function. Neuropathologically, it is characterized by the presence of extracellularβ-amyloid (Aβ) deposited as neuritic plaques (NP) and neurofibrillary tangles (NFT) made of abnormal and hyperphosphorylated tau protein. These lesions are capable of generating the neuronal damage that leads to cell death and cognitive failure through the generation of reactive oxygen species (ROS). Evidence indicates the critical role of Aβmetabolism in prompting the oxidative stress observed in AD patients. However, it has also been proposed that oxidative damage precedes the onset of clinical and pathological AD symptoms, including amyloid-βdeposition, neurofibrillary tangle formation, vascular malfunction, metabolic syndrome, and cognitive decline. This paper provides a brief description of the three main proteins associated with the development of the disease (Aβ, tau, and ApoE) and describes their role in the generation of oxidative stress. Finally, we describe the mitochondrial alterations that are generated by Aβand examine the relationship of vascular damage which is a potential prognostic tool of metabolic syndrome. In addition, new therapeutic approaches targeting ROS sources and metabolic support were reported.

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

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4410 ◽  
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.

Oxidative Stress, Metabolic Syndrome and Alzheimer’s Disease

2016 ◽  
pp. 361-374 ◽  
Author(s):  
Danira Toral-Rios ◽  
Karla Carvajal ◽  
Bryan Phillips-Farfán ◽  
Luz del Carmen Camacho-Castillo ◽  
Victoria Campos-Peña
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metabolic Syndrome

Oxidative Stress Targeting Amyloid Beta Accumulation and Clearance in Alzheimer’s Disease: Insight into Pathological Mechanisms and Therapeutic Strategies

2020 ◽  
Vol 9 (1) ◽  
pp. 22-42
Author(s):  
Sunpreet Kaur ◽  
Puneet Kumar ◽  
Shamsher Singh
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neurodegenerative Disorder ◽  
Acetylcholinesterase Inhibitors ◽  
The Elderly ◽  
Biochemical Alterations ◽  
App Trafficking ◽  
Copper Aluminum

Background: Alzheimer’s disease is the most common neurodegenerative disorder affecting the elderly population and emerges as a leading challenge for the scientific research community. The wide pathological aspects of AD made it a multifactorial disorder and even after long time it’s difficult to treat due to unexplored etiological factors. Methods: The etiogenesis of AD includes mitochondrial failure, gut dysbiosis, biochemical alterations but deposition of amyloid-beta plaques and neurofibrillary tangles are implicated as major hallmarks of neurodegeneration in AD. The aggregates of these proteins disrupt neuronal signaling, enhance oxidative stress and reduce activity of various cellular enzymes which lead to neurodegeneration in the cerebral cortex, neocortex and hippocampus. The metals like copper, aluminum are involved in APP trafficking and promote amyloidbeta aggregation. Similarly, disturbed ubiquitin proteasomal system, autophagy and amyloid- beta clearance mechanisms exert toxic insult in the brain. Result and conclusion : The current review explored the role of oxidative stress in disruption of amyloid homeostasis which further leads to amyloid-beta plaque formation and subsequent neurodegeneration in AD. Presently, management of AD relies on the use of acetylcholinesterase inhibitors, antioxidants and metal chelators but they are not specific measures. Therefore, in this review, we have widely cited the various pathological mechanisms of AD as well as possible therapeutic targets.

Drugs for Targeted Therapies of Alzheimer’s Disease

2019 ◽  
Vol 26 (2) ◽  
pp. 335-359 ◽  
Author(s):  
Chit Tam ◽  
Jack Ho Wong ◽  
Tzi Bun Ng ◽  
Stephen Kwok Wing Tsui ◽  
Tao Zuo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Drug Targets ◽  
The Elderly ◽  
Dependent Manner ◽  
Cell Replacement Therapy ◽  
Drug Candidates ◽  
Amyloid A ◽  
Potential Drug Targets

Alzheimer’s disease (AD) is one type of neurodegenerative diseases, which is prevalent in the elderly. Beta-amyloid (Aβ) plaques and phosphorylated tau-induced neurofibrillary tangles are two pathological hallmarks of this disease and the corresponding pathological pathways of these hallmarks are considered as the therapeutic targets. There are many drugs scheduled for pre-clinical and clinical trial that target to inhibit the initiators of pathological Aβ and tau aggregates as well as critical Aβ secretases and kinases in tau hyperphosphorylation. In addition, studies in disease gene variations, and detection of key prognostic effectors in early development are also important for AD control. The discovery of potential drug targets contributed to targeted therapy in a stage-dependent manner, However, there are still some issues that cause concern such as the low bioavailability and low efficacy of candidate drugs from clinical trial reports. Therefore, modification of drug candidates and development of delivery agents are essential and critical. With other medical advancements like cell replacement therapy, there is hope for the cure of Alzheimer’s disease in the foreseeable future.

scholarly journals P-glycoprotein (ABCB1) and Oxidative Stress: Focus on Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Giulia Sita ◽  
Patrizia Hrelia ◽  
Andrea Tarozzi ◽  
Fabiana Morroni
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Drug ◽  
Amyloid A ◽  
P Glycoprotein ◽  
And Function ◽  
The Brain ◽  
Brain Homeostasis

ATP-binding cassette (ABC) transporters, in particular P-glycoprotein (encoded by ABCB1), are important and selective elements of the blood-brain barrier (BBB), and they actively contribute to brain homeostasis. Changes in ABCB1 expression and/or function at the BBB may not only alter the expression and function of other molecules at the BBB but also affect brain environment. Over the last decade, a number of reports have shown that ABCB1 actively mediates the transport of beta amyloid (Aβ) peptide. This finding has opened up an entirely new line of research in the field of Alzheimer’s disease (AD). Indeed, despite intense research efforts, AD remains an unsolved pathology and effective therapies are still unavailable. Here, we review the crucial role of ABCB1 in the Aβtransport and how oxidative stress may interfere with this process. A detailed understanding of ABCB1 regulation can provide the basis for improved neuroprotection in AD and also enhanced therapeutic drug delivery to the brain.

Protective Effect of Kaempferol on the Transgenic Drosophila Model of Alzheimer’s Disease

2018 ◽  
Vol 17 (6) ◽  
pp. 421-429 ◽  
Author(s):  
Tanveer Beg ◽  
Smita Jyoti ◽  
Falaq Naz ◽  
Rahul ◽  
Fahad Ali ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neuronal Damage ◽  
Natural Antioxidants ◽  
Acetylcholinesterase Activity ◽  
Model Of Alzheimer’S Disease ◽  
Climbing Ability ◽  
Transgenic Drosophila

Background: Alzheimer’s disease (AD) is characterized by the accumulation and deposition of β-amyloid peptides leading to a progressive neuronal damage and cell loss. Besides several hypotheses for explaining the neurodegenerative mechanisms, oxidative stress has been considered to be one of them. Till date, there is no cure for AD, but the pathogenesis of the disease could be delayed by the use of natural antioxidants. In this context, we decided to study the effect of kaempferol against the transgenic Drosophila expressing human amyloid beta-42. Method: The AD flies were allowed to feed on the diet having 10, 20, 30 and 40µM of kaempferol for 30 days. After 30 days of exposure, the amyloid beta flies were studied for their climbing ability and Aversive Phototaxis Suppression assay. Amyloid beta flies head homogenate was prepared for estimating the oxidative stress markers, Caspase and acetylcholinesterase activity. Results: The results of the present study reveal that the exposure of AD flies to kaempferol delayed the loss of climbing ability, memory, reduced the oxidative stress and acetylcholinesterase activity. Conclusion: Kaempferol could be used as a possible therapeutic agent against the progression of the Alzheimer’s disease.

scholarly journals The emerging possibility of the use of geniposide in the treatment of cerebral diseases: a review

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wenwen Zhang ◽  
Fangling Zhang ◽  
Qichao Hu ◽  
Xiaolin Xiao ◽  
Linbo Ou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Ischaemia ◽  
Neuronal Damage ◽  
Biological Activities ◽  
Protective Effects ◽  
Specific Circumstance ◽  
Gardenia Jasminoides ◽  
Cerebral Diseases

AbstractWith the advanced discoveries in the field of pathogenesis, a series of cerebral diseases, such as cerebral ischaemia, Alzheimer's disease, and depression, have been found to have multiple signalling targets in the microenvironment. Only a few existing agents have been shown to have curative effects due to this specific circumstance. In recent decades, active ingredients isolated from natural plants have been shown to be crucial for original drug development. Geniposide, mainly extracted from Gardenia jasminoides Ellis, is representative of these natural products. Geniposide demonstrates various biological activities in the treatment of cerebral, cardiovascular, hepatic, tumorous, and other diseases. The multiple protective effects of geniposide on the brain have especially drawn increasing attention. Thus, this article specifically reviews the characteristics of current models of cerebral ischaemia and illustrates the possible effects of geniposide and its pathogenetic mechanisms on these models. Geniposide has been shown to significantly reduce the area of cerebral infarction and alleviate neuronal damage and necrosis mainly by inhibiting inflammatory signals, including NLRP3, TNF-α, IL-6, and IL-1β. Neuronal protection was also involved in activating the PI3K/Akt and Wnt/catenin pathways. Geniposide was able to increase autophagy and inhibit apoptosis by regulating the function of mTOR in treating Alzheimer's disease. Geniposide has also been shown to act as a glucagon-like peptide-1 receptor (GLP-1R) agonist to reduce amyloid plaques and inhibit oxidative stress to alleviate memory impairment as well as synaptic loss. Moreover, geniposide has been shown to exert antidepressant effects primarily by regulating the hypothalamic–pituitary–adrenal (HPA) axis. Detailed explorations have shown that the biological activities of inhibiting inflammatory cytokine secretion, alleviating oxidative stress, and suppressing mitochondrial damage are also involved in the mechanism of action of geniposide. Therefore, geniposide is a promising agent awaiting further exploration for the treatment of cerebral diseases via various phenotypes or signalling pathways.

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

Antioxidants ◽  
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.

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration

Synapse ◽  
2017 ◽  
Vol 71 (10) ◽  
pp. e21990 ◽  
Author(s):  
Eduardo Rojas-Gutierrez ◽  
Guadalupe Muñoz-Arenas ◽  
Samuel Treviño ◽  
Blanca Espinosa ◽  
Raúl Chavez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metabolic Syndrome

Mitochondrial perturbation drives tau oligomers pathology in Alzheimer’s disease

2020 ◽  
Author(s):  
Fang DU ◽  
Qing Yu ◽  
Doris Chen ◽  
Shi Fang Yan ◽  
Shirley Yan
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ex Vivo ◽  
Neuronal Cells ◽  
Neurofibrillary Tangle ◽  
Contributing Factors ◽  
Tau Oligomers ◽  
Oligomer Formation ◽  
Underlying Mechanisms

Abstract Tau oligomers, prior to neurofibrillary tangle formation, are toxic species responsible for tau pathology, mitochondrial and synaptic damage, and memory impairment. The underlying mechanisms of abnormal tau accumulation and strategies to eliminate them remain largely unknown. The present study addresses whether mitochondrial reactive oxygen species (ROS) are major contributing factors for tau oligomer formation and, if so, whether eliminating mitochondrial ROS reduces accumulation of tau oligomers and improves mitochondrial and cognitive function in Alzheimer’s disease (AD). First, we determined whether increased oxidative stress correlates with aggregation of tau oligomers in human AD-affected brains, Aβ/tau overexpressed mouse models, human trans-mitochondrial “cybrid” (cytoplasmic hybrid) neuronal cells containing mild cognitive impairment (MCI) and AD-derived mitochondria, and Aβ/tau expressing neuronal cells. In P301S tau and AD mice, upregulation of tau oligomers correlates with ROS accumulation. Elevated tau oligomer levels are also correlated with elevated ROS levels in the AD patient hippocampus. Importantly, human cybrid cells, whose mitochondria are derived from platelets of patients with sporadic AD or MCI, displayed aggregated tau oligomers, which also correlated with upregulated ROS levels. Application of mito-Tempo, a mitochondria-targeted antioxidant, to inhibit the generation of mitochondrial and intracellular ROS in tau and AD neurons, as well as in MCI and AD cybrids ex vivo, leads to a striking decrease in tau oligomers. Finally, in AD mice, mito-Tempo inhibited tau oligomer accumulation and improved behavioral deficiency. Our work adds to the growing body of evidence that oxidative stress contributes to tau oligomer formation and that inhibition of oxidative stress ameliorates tauopathy in AD.

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