scholarly journals APOE4, oxidative stress and decreased repair capacity - a no-brainer. Faulty lipid metabolism and increased levels of oxidative damage may be risk factors in the pathogenesis of late-onset dementia

Biodiscovery ◽  
2015 ◽  
pp. 1 ◽  
Author(s):  
Ashima Nayyar ◽  
◽  
Lubomira Chakalova ◽  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Lipid Metabolism ◽  
Oxidative Damage ◽  
Late Onset ◽  
Repair Capacity ◽  
Late Onset Dementia

scholarly journals Linoleic acid, α-linolenic acid and enterolactone affect lipid oxidation and expression of lipid metabolism and antioxidant-related genes in hepatic tissue of dairy cows

2017 ◽  
Vol 117 (9) ◽  
pp. 1199-1211 ◽  
Author(s):  
Émilie Fortin ◽  
Richard Blouin ◽  
Jérôme Lapointe ◽  
Hélène V. Petit ◽  
Marie-France Palin
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Lipid Metabolism ◽  
Linoleic Acid ◽  
Oxidative Damage ◽  
Dairy Cows ◽  
Linolenic Acid ◽  
Target Genes ◽  
Culture Media ◽  
Oxidative Damages

AbstractAlthough beneficial effects have been attributed to PUFA supplementation in high-yielding dairy cows, diets rich in PUFA may also increase oxidative stress in tissues such as the liver. To fully exploit the health benefits of PUFA, we believe that the addition of natural antioxidants could help in preventing oxidative damage. Using an in vitro precision-cut liver slices (PCLS) tissue culture system, we investigated the effects of different linoleic acid (LA, n-6):α-linolenic acid (ALA, n-3) ratios (LA:ALA ratio of 4, LA:ALA ratio of 15 and LA:ALA ratio of 25) in the presence or absence of the antioxidant enterolactone (ENL) on (1) the mRNA abundance of genes with key roles in hepatic lipid metabolism, oxidative stress response and inflammatory processes, (2) oxidative damages to lipids and proteins and (3) superoxide dismutase activity in early-lactating dairy cows. The addition of LA and ALA to PCLS culture media increased oxidative damage to lipids as suggested by higher concentrations of thiobarbituric acid reactive substances and increased the expression of nuclear factor erythroid 2-related factor 2 target genes. The addition of ENL was effective in preventing lipid peroxidation caused by LA and ALA. Transcript abundance of sterol regulatory element-binding transcription factor 1 and its lipogenic target genes acetyl-CoA carboxylase α, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) was decreased with LA and ALA, whereas ENL decreased FASN and SCD gene expression. Our results show that addition of LA and ALA to PCLS culture media lowers hepatic lipogenic gene expression and increases oxidative damages to lipids. On the other hand, addition of ENL prevents oxidative damages provoked by these PUFA.

scholarly journals Saccharomyces cerevisiae Cytosolic Thioredoxins Control Glycolysis, Lipid Metabolism, and Protein Biosynthesis under Wine-Making Conditions

2019 ◽  
Vol 85 (7) ◽  
Author(s):  
Cecilia Picazo ◽  
Brian McDonagh ◽  
José Peinado ◽  
José A. Bárcena ◽  
Emilia Matallana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Lipid Metabolism ◽  
Amino Acid ◽  
Oxidative Damage ◽  
Mutant Strain ◽  
Grape Juice ◽  
Wine Yeast ◽  
Content Type ◽  
Small Proteins

ABSTRACT Thioredoxins are small proteins that regulate the cellular redox state, prevent oxidative damage, and play an active role in cell repair. Oxidative stress has proven to be of much relevance in biotechnological processes when the metabolism of Saccharomyces cerevisiae is mainly respiratory. During wine yeast starter production, active dry yeast cytosolic thioredoxin Trx2p is a key player in protecting metabolic enzymes from being oxidized by carbonylation. Less is known about the role of redox control during grape juice fermentation. A mutant strain that lacked both cytosolic thioredoxins, Trx1p and Trx2p, was tested for grape juice fermentation. Its growth and sugar consumption were greatly impaired, which indicates the system’s relevance under fermentative conditions. A proteomic analysis indicated that deletion of the genes TRX1 and TRX2 caused a reduction in the ribosomal proteins and factors involved in translation elongation in addition to enzymes for glycolysis and amino acid biosynthesis. A metabolomic analysis of the trx1Δ trx2Δ mutant showed an increase in most proteogenic amino acids, phospholipids, and sphingolipids and higher fatty acid desaturase Ole1p content. Low glycolytic activity was behind the reduced growth and fermentative capacity of the thioredoxin deletion strain. All three hexokinases were downregulated in the mutant strain, but total hexokinase activity remained, probably due to posttranslational regulation. Pyruvate kinase Cdc19p presented an early level of aggregation in the trx1Δ trx2Δ mutant, which may contribute to a diminished hexose metabolism and trigger regulatory mechanisms that could influence the level of glycolytic enzymes. IMPORTANCE Oxidative stress is a common hazardous condition that cells have to face in their lifetime. Oxidative damage may diminish cell vitality and viability by reducing metabolism and eventually leading to aging and ultimate death. Wine yeast Saccharomyces cerevisiae also faces oxidative attack during its biotechnological uses. One of the main yeast antioxidant systems involves two small proteins called thioredoxins. When these two proteins are removed, wine yeast shows diminished growth, protein synthesis, and sugar metabolism under wine-making conditions, and amino acid and lipid metabolism are also affected. Altogether, our results indicate that proper redox regulation is a key factor for metabolic adaptations during grape juice fermentation.

scholarly journals Nanotargeting of Drug(s) for Delaying Dementia: Relevance of Covid-19 Impact on Dementia

2020 ◽  
Vol 35 ◽  
pp. 153331752097676
Author(s):  
Joseph S. D’Arrigo
Keyword(s):  
Risk Factors ◽  
Memory Impairment ◽  
Late Onset ◽  
Scavenger Receptors ◽  
Type I ◽  
Human Coronavirus ◽  
Memory Decline ◽  
Class B ◽  
Lipid Nanocarriers ◽  
Late Onset Dementia

By incorporating appropriate drug(s) into lipid (biobased) nanocarriers, one obtains a combination therapeutic for dementia treatment that targets certain cell-surface scavenger receptors (mainly class B type I, or “SR-BI”) and thereby crosses the blood-brain barrier. The cardiovascular risk factors for dementia trigger widespread inflammation -- which lead to neurodegeneration, gradual cognitive/memory decline, and eventually (late-onset) dementia. Accordingly, one useful strategy to delay dementia could be based upon nanotargeting drug(s), using lipid nanocarriers, toward a major receptor class responsible for inflammation-associated (cytokine-mediated) cell signaling events. At the same time, the immune response and excessive inflammation, commonly observed in the very recent human coronavirus (COVID-19) pandemic, may accelerate the progression of brain inflammatory neurodegeneration—which increases the probability of post-infection memory impairment and accelerating progression of Alzheimer’s disease. Hence, the proposed multitasking combination therapeutic, using a (biobased) lipid nanocarrier, may also display greater effectiveness at different stages of dementia.

scholarly journals Age-Related Neuronal Deterioration Specifically Within the Dorsal CA1 Region of the Hippocampus in a Mouse Model of Late Onset Alzheimer’s Disease

2021 ◽  
Vol 79 (4) ◽  
pp. 1547-1561
Author(s):  
Rasha H. Mehder ◽  
Brian M. Bennett ◽  
R. David Andrew
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Peroxidation ◽  
Mouse Model ◽  
Oxidative Damage ◽  
Late Onset ◽  
Dendritic Morphology ◽  
Ca1 Region ◽  
Age Related

Background: Neuronal damage resulting from increased oxidative stress is important in the development of late onset/age-related Alzheimer’s disease (LOAD). We have developed an oxidative stress–related mouse model of LOAD based on gene deletion of aldehyde dehydrogenase 2 (ALDH2), an enzyme important for the detoxification of endogenous aldehydes arising from lipid peroxidation. Compared to wildtype (WT) mice, the knockout (KO) mice exhibit AD-like pathologies and a progressive decline in recognition and spatial memory. This progression presumably has a morphological basis induced by oxidative damage. Objective: We performed morphometric analyses in the dorsal hippocampal CA1 region (dCA1) to determine if altered neuronal structure can help account for the progressive cognitive impairment in 3- to 12-month-old KO mice. Methods: Dendritic morphology was quantitatively analyzed by branched structured analysis and Sholl analysis following Golgi-Cox staining in WT mice (148 neurons) versus KO mice (180 neurons). Results: The morphology and complexity of dCA1 pyramidal neurons were similar at age 3 months in WTs and KOs. However, by 6 months there were significant reductions in apical and basal dendritic length, dendrite complexity, and spine density in KO versus WT mice that were maintained through ages 9 and 12 months. Immunostaining for protein adducts of the lipid peroxidation product 4-hydroxynonenal revealed significant increases in staining in dCA1 (but not ventral CA1) by 3 months, increasing through 12 months. Conclusion: This specific and progressive increase in dCA1 oxidative damage preceded detectable synaptic trimming in KO mice, in keeping with studies showing that lesions to dorsal hippocampus primarily impair cognitive memory.

scholarly journals Suicidal Ideations and Behavior in Patients With Young and Late Onset Dementia

2021 ◽  
Vol 12 ◽  
Author(s):  
Marion Ortner ◽  
Lina Riedl ◽  
Ralf J. Jox ◽  
Julia Hartmann ◽  
Carola Roßmeier ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Function ◽  
Suicidal Ideation ◽  
Suicidal Behavior ◽  
Late Onset ◽  
Physical Symptoms ◽  
Advanced Dementia ◽  
Death Wishes ◽  
And Behavior ◽  
Late Onset Dementia

Background and Objectives: Data on suicidal ideation, behavior and the risk factors in patients with dementia is scarce. To evaluate the prevalence of death wishes, suicidal ideation, and suicidal behavior of young (YOD) and late onset dementia (LOD) and to identify risk factors for suicidal ideation and behavior.Methods: We interviewed 157 family caregivers of patients with advanced dementia using questions from the Columbia-Suicide Severity Rating Scale to gather information about suicidal ideation and behavior before the onset of symptoms of dementia, after the onset of dementia and within 30 days prior to the interview. At the time of the interview, we also assessed disease severity, cognitive function, and other psychological, behavioral and physical symptoms of the patients as well as the caregivers' psychological well-being.Results: Forty four (28%) of the patients expressed suicidal ideation or behavior at some time after the onset of symptoms, and 14 (9%) of these within the month prior to the assessment. Two patients had attempted suicide after the onset of dementia. There were no statistically significant differences between patients with and without suicidal ideations or behavior with regards to demographics or age at onset of dementia. In patients with advanced dementia, Alzheimer's disease (rather than frontotemporal lobar degeneration), better cognitive function, more severe psychological, behavioral, and physical symptoms, and a reduced quality of life were associated with the expression of suicidal ideation.Conclusions: According to caregivers' reports, majority of patients with dementia did not express suicidal ideation or show suicidal behavior. Patients who expressed suicidal ideation during early stages of dementia often stopped expressing them in advanced stages. It remains unclear if this was due to reduced communication abilities, a reduction of disease awareness, and/ or an adjustment to their situation.

scholarly journals Lifestyle risk Factors for early versus late onset dementia: A systematic review and meta-analysis

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
N Berselli ◽  
G Adani ◽  
T Filippini ◽  
M Vinceti
Keyword(s):  
Risk Factors ◽  
Brain Injuries ◽  
Age Of Onset ◽  
Late Onset ◽  
Meta Analysis ◽  
Lifestyle Risk Factors ◽  
Modifiable Factors ◽  
Lifestyle Risk ◽  
The Impact ◽  
Late Onset Dementia

Abstract Background Dementia is a widely prevalent and growing condition, affecting nearly 10% of people aged 60 years and older. It is a leading cause of disability entailing important economic and social costs for the population, so much so that it has been defined as a “global public health priority' from WHO in 2016. Dementia can be divided into two forms according to age of onset of the first symptoms: Early Onset Dementia (EOD - < 65 years) and Late Onset Dementia (LOD, ≥ 65 years). The differences between the two forms, and if they could be considered as separate diseases, are still not well understood. The aim of this meta-analysis was to determine if environmental-lifestyle risk factors of dementia may differ between EOD and LOD. Methods Literature databases were searched to June 2020, to retrieve studies assessing the impact of modifiable factors in patients who had developed the first symptoms of dementia before (for EOD) or after (for LOD) 65 years. Data were then meta-analysed in order to understand the overall impact of the single factors on EOD and LOD separately. Results The results show different effects for some risk factors as alcohol consumption (OR 2.8, 95%CI: 2.2-3.4 for EOD and OR 1.2, 95%CI: 0.9-1.5 for LOD) and brain injuries (OR 1.4, 95%CI: 1.2-1.6 for EOD, and OR 1, 95%CI: 0.6-1.4 for LOD), which appear to have more impact on EOD compared with LOD. No association with smoking for both forms of dementia emerged. The other factors considered, such as low educational attainment, socio-economic status, closeness of magnetic field, appear to have similar impact on the two forms of dementia. Conclusions These results suggest that there may be a difference, in terms of modifiable risk factors, between the two forms of dementia, even if more research is needed on this issue. Key messages There may be different risk factors determining EOD versus LOD onset. By modifying some environmental and lifestyle factors we could delay or prevent the onset of dementia.

scholarly journals Effective interventions for potentially modifiable risk factors for late-onset dementia: a costs and cost-effectiveness modelling study

2020 ◽  
Vol 1 (1) ◽  
pp. e13-e20 ◽  
Author(s):  
Naaheed Mukadam ◽  
Robert Anderson ◽  
Martin Knapp ◽  
Raphael Wittenberg ◽  
Maria Karagiannidou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cost Effectiveness ◽  
Late Onset ◽  
Modifiable Risk Factors ◽  
Effective Interventions ◽  
Late Onset Dementia ◽  
Modelling Study

Oxidative injury associated with stenting of asymptomatic carotid artery stenosis

VASA ◽  
2017 ◽  
Vol 46 (4) ◽  
pp. 268-274
Author(s):  
Erhan Saraçoğlu ◽  
Ertan Vuruşkan ◽  
Yusuf Çekici ◽  
Salih Kiliç ◽  
Halil Ay ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carotid Artery ◽  
Oxidative Damage ◽  
Carotid Artery Stenosis ◽  
Artery Stenosis ◽  
Oxidative Stress Marker ◽  
Asymptomatic Carotid ◽  
Imaging Methods ◽  
Neurological Findings ◽  
Asymptomatic Carotid Artery Stenosis

Abstract. Background: After carotid artery stenting (CAS), neurological complications that cannot be explained with imaging methods may develop. In our study we aimed to show, using oxidative stress markers, isolated oxidative damage and resulting neurological findings following CAS in patients with asymptomatic carotid artery stenosis. Patients and methods: We included 131 neurologically asymptomatic patients requiring CAS. The neurological findings were evaluated using the modified Rankin Scale (mRS) prior to the procedure, one hour post-procedure, and two days after. Patients with elevated mRS scores but with or without typical hyperintense lesions observed on an MRI and with changes of oxidative stress marker levels at the time (Δtotal-thiol, Δtotal antioxidative status [TAS], and Δtotal oxidant status [TOS]) were evaluated. Results: In the neurological examination carried out one hour prior to the procedure, there were 92 patients with mRS = 0, 20 with mRS = 1, and 12 with mRS = 2. When Δtotal-thiol, ΔTAS, and ΔTOS values and the mRS were compared, it was observed that as the difference in oxidative parameters increased, clinical deterioration also increased proportionally (p = 0.001). Conclusions: We demonstrate a possible correlation between oxidative damage and neurological findings after CAS which could not be explained by routine imaging methods.

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