scholarly journals Interplay Between Oxidative Damage, Protein Synthesis, and Protein Degradation in Alzheimer's Disease

2006 ◽  
Vol 2006 ◽  
pp. 1-3 ◽  
Author(s):  
Jeffrey N. Keller
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Synthesis ◽  
Steady State ◽  
Oxidative Damage ◽  
Cell Viability ◽  
Protein Degradation ◽  
Cellular Processes ◽  
Damage Protein

Protein synthesis and protein degradation are highly regulated cellular processes that are essential to maintaining cell viability. Numerous studies now indicate that protein synthesis and protein degradation are significantly altered in Alzheimer's disease (AD), with impairments in these two processes potentially contributing to AD pathogenesis. Alterations in steady state protein regulation may be a particularly important factor in regulating whether cells maintain homeostasis in response to oxidative damage, or conversely whether oxidative stress is induced by oxidative damage. The focus of this review is to discuss recent findings on each of these topics, and to discuss their importance to the onset and progression of AD.

Silibinin-Albumin Nanoparticles: Characterization and Biological Evaluation Against Oxidative Stress-Stimulated Neurotoxicity Associated with Alzheimer’s Disease

2021 ◽  
Vol 17 (6) ◽  
pp. 1123-1130
Author(s):  
Qichen Pan ◽  
Yunchao Ban ◽  
Lijun Xu
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant Activity ◽  
Cell Viability ◽  
Antioxidant Activities ◽  
Drug Loading ◽  
Biological Evaluation ◽  
Neural Cells ◽  
Nanoparticles Characterization

Alzheimer’s disease (AD) is strongly associated with oxidative stress which can damage neural cells. Silibinin has shown potential antioxidative effects. However, due to its low solubility in water, silibinin provides low biological activity and bioavailability. Therefore, to increase its pharmacological effects, silibilin was encapsulated into human serum albumin (HSA) nanoparticles and well-characterized by DLS and TEM techniques. The antioxidant activity of silibinin-HSA nanoparticles was evaluated on LPS-induced oxidative stress in neuron-like cells (SH-SY5Y) through MTT, antioxidant activity and apoptotic assay. It was shown that the mean diameter of HSA and silibinin-HSA nanoparticles were 88 and 105 nm, respectively with a drug loading of 24.08%, drug encapsulation rate of 94.72%, and the yield of silibinin-HSA nanoparticles of around 83.41% and the HSA nano-formulation released silibinin for 15 h. The results displayed that cell viability was reduced by LPS (10 μg/mL), who’s also determined to stimulate oxidative stress and apoptosis. However, co-incubation of cells with silibinin (50 μg/mL) or silibinin-HSA nanoparticles led to the recovery of cell viability, activation of SOD and CAT, increase of GSH content, and reduction of ROS level, Caspase-3 activity and fragmentation of DNA. It was also indicated that the neuroprotective and antioxidant activities of silibinin-HAS nanoparticles was greater than free silibinin, indicating that using albumin can be a potential formulation approach for improving the antioxidant efficacy of silibinin.

scholarly journals Redox proteomics analysis to decipher the neurobiology of Alzheimer-like neurodegeneration: overlaps in Down's syndrome and Alzheimer's disease brain

2014 ◽  
Vol 463 (2) ◽  
pp. 177-189 ◽  
Author(s):  
D. Allan Butterfield ◽  
Fabio Di Domenico ◽  
Aaron M. Swomley ◽  
Elizabeth Head ◽  
Marzia Perluigi
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Damage ◽  
Protein Function ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Post Translational Modifications ◽  
Redox Proteomics ◽  
Age Related

Accumulation of oxidative damage is a common feature of neurodegeneration that, together with mitochondrial dysfunction, point to the fact that reactive oxygen species are major contributors to loss of neuronal homoeostasis and cell death. Among several targets of oxidative stress, free-radical-mediated damage to proteins is particularly important in aging and age-related neurodegenerative diseases. In the majority of cases, oxidative-stress-mediated post-translational modifications cause non-reversible modifications of protein structure that consistently lead to impaired function. Redox proteomics methods are powerful tools to unravel the complexity of neurodegeneration, by identifying brain proteins with oxidative post-translational modifications that are detrimental for protein function. The present review discusses the current literature showing evidence of impaired pathways linked to oxidative stress possibly involved in the neurodegenerative process leading to the development of Alzheimer-like dementia. In particular, we focus attention on dysregulated pathways that underlie neurodegeneration in both aging adults with DS (Down's syndrome) and AD (Alzheimer's disease). Since AD pathology is age-dependent in DS and shows similarities with AD, identification of common oxidized proteins by redox proteomics in both DS and AD can improve our understanding of the overlapping mechanisms that lead from normal aging to development of AD. The most relevant proteomics findings highlight that disturbance of protein homoeostasis and energy production are central mechanisms of neurodegeneration and overlap in aging DS and AD. Protein oxidation affects crucial intracellular functions and may be considered a ‘leitmotif’ of degenerating neurons. Therapeutic strategies aimed at preventing/reducing multiple components of processes leading to accumulation of oxidative damage will be critical in future studies.

Oxidative Damage of Proteins Precedes Loss of Cholinergic Phenotype in the Septal Neurons of Olfactory Bulbectomized Mice

2021 ◽  
Vol 19 ◽  
Author(s):  
O.A. Nedogreeva ◽  
N.A. Evtushenko ◽  
A.O. Manolova ◽  
D.I. Peregud ◽  
A.A. Yakovlev ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Damage ◽  
Cognitive Decline ◽  
Water Maze ◽  
Neuronal Damage ◽  
Cholinergic Neurons ◽  
Olfactory Bulbectomy ◽  
Cholinergic Dysfunction

Background: The development of cholinergic deficit is considered an early sign of a number of pathological conditions, including Alzheimer’s disease. Cholinergic dysfunction underlies cognitive decline associated with both normal aging and Alzheimer’s disease. Objective: Here, we studied a possible mechanism of functional impairment of cholinergic neurons using an olfactory bulbectomy model. Methods: Male mice were subjected to olfactory bulbectomy or sham surgery. Three weeks after that they were trained in Morris water maze and then euthanized one month after surgery. The cholinergic indices as well as the indices of oxidative stress were studied using immunohistochemistry, western blot and ELISA. Gene expression was studied using RT-qPCR. Results: The experimental treatment was followed by impaired learning of a standard spatial task in a water maze. This was associated with a decrease in the number of cells containing choline acetyltransferase (ChAT), in relation to total number of neurons in the medial septum and lower ChAT enzymatic activity in the hippocampus. However, the levels of mRNAs of ChAT, vesicular ACh transporter and acetylcholine esterase remained unchanged in bulbectomized mice compared to sham-operated animals. These alterations were preceded by the accumulation of protein-bound carbonyls, indicating oxidative damage of proteins, whereas oxidative damage of nucleic acids was not detected. Conclusion: We assume that in olfactory bulbectomy model, oxidative damage of proteins may cause cholinergic dysfunction rather than irreversible neuronal damage. These data indicate that cholinergic neurons of the basal forebrain are very sensitive to oxidative stress, which may be responsible for the appearance of early cognitive decline in Alzheimer’s disease.

scholarly journals Tortoise Plastron and Deer Antler Gelatin Prevents Against Neuronal Mitochondrial Dysfunction In Vitro: Implication for a Potential Therapy of Alzheimer’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Dan Cheng ◽  
Xin-Jing Yang ◽  
Lu Zhang ◽  
Zong-Shi Qin ◽  
Wen-Qi Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Damage ◽  
Cell Viability ◽  
Mitochondrial Dysfunction ◽  
Dependent Manner ◽  
Deer Antler ◽  
Mitochondrial Dynamic ◽  
Aberrant Expression

Mitochondrial dysfunction with oxidative damage plays the fundamental roles in the pathogenesis of Alzheimer’s disease. In traditional Chinese medicine (TCM) practice, animal tissue-derived gelatins are often used as nootropic agents to treat cognitive deterioration and senile dementia. Tortoise plastron gelatin (TPG) and deer antler gelatin (DAG) are the two most commonly used gelatins for this purpose. This study sought to examine the effects of the two gelatins in preventing neuronal mitochondria from oxidative damage. PC12 cells, a cell line derived from rat pheochromocytoma, exposed to the neurotoxin Aβ25–35 served as an in vitro model of Alzheimer’s disease. The cells were separately pre-treated with TPG and DAG at various concentrations ranging from 6.26 µg/ml–200 µg/ml, followed by co-incubation with 20 μM Aβ25–35 for different duration. Cell viability, mitochondrial membrane potential (MMP) and ultrastructure, intracellular ATP, reactive oxygen species (ROS) and calcium (Ca2+) level, the expression of mitochondrial dynamic proteins and biomarkers of apoptosis were measured. Pretreatment with TPG and DAG reversed the Aβ-induced reduction of cell viability in a dose-dependent manner. Both TPG and DAG significantly increased MMP and ATP, alleviated the accumulation of damaged mitochondrial fragments, and normalized the aberrant expression of multiple mitochondrial dynamic proteins of the Aβ-exposed cells. Both gelatins also suppressed intracellular ROS overproduction and Ca2+ overload, overexpression of cytochrome c and pro-apoptosis biomarkers induced by the Aβ exposure. These results suggest that TPG and DAG may have the anti-dementia potential by preventing neuronal mitochondria from oxidative damage.

scholarly journals Multiple Herpes Simplex Virus-1 (HSV-1) Reactivations Induce Protein Oxidative Damage in Mouse Brain: Novel Mechanisms for Alzheimer’s Disease Progression

2020 ◽  
Vol 8 (7) ◽  
pp. 972 ◽  
Author(s):  
Virginia Protto ◽  
Antonella Tramutola ◽  
Marco Fabiani ◽  
Maria Elena Marcocci ◽  
Giorgia Napoletani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Oxidative Damage ◽  
Mouse Brain ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

Compelling evidence supports the role of oxidative stress in Alzheimer’s disease (AD) pathophysiology. Interestingly, Herpes simplex virus-1 (HSV-1), a neurotropic virus that establishes a lifelong latent infection in the trigeminal ganglion followed by periodic reactivations, has been reportedly linked both to AD and to oxidative stress conditions. Herein, we analyzed, through biochemical and redox proteomic approaches, the mouse model of recurrent HSV-1 infection we previously set up, to investigate whether multiple virus reactivations induced oxidative stress in the mouse brain and affected protein function and related intracellular pathways. Following multiple HSV-1 reactivations, we found in mouse brains increased levels of oxidative stress hallmarks, including 4-hydroxynonenal (HNE), and 13 HNE-modified proteins whose levels were found significantly altered in the cortex of HSV-1-infected mice compared to controls. We focused on two proteins previously linked to AD pathogenesis, i.e., glucose-regulated protein 78 (GRP78) and collapsin response-mediated protein 2 (CRMP2), which are involved in the unfolded protein response (UPR) and in microtubule stabilization, respectively. We found that recurrent HSV-1 infection disables GRP78 function and activates the UPR, whereas it prevents CRMP2 function in mouse brains. Overall, these data suggest that repeated HSV-1 reactivation into the brain may contribute to neurodegeneration also through oxidative damage.

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 Is ascorbate Dr Jekyll or Mr Hyde in the Cu(Aβ) mediated oxidative stress linked to Alzheimer's disease?

2016 ◽  
Vol 45 (32) ◽  
pp. 12627-12631 ◽  
Author(s):  
Clémence Cheignon ◽  
Fabrice Collin ◽  
Peter Faller ◽  
Christelle Hureau
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Damage ◽  
Ros Production ◽  
High Concentration ◽  
Low Concentration ◽  
Biological Targets

At low concentration, ascorbate promotes oxidative damageviaCu(Aβ) induced ROS production while at high concentration it can prevent oxidation of biological targets other than Aβ itself.

scholarly journals Oxidative Stress during the Progression ofβ-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Sara Porcellotti ◽  
Francesca Fanelli ◽  
Anna Fracassi ◽  
Sara Sepe ◽  
Francesco Cecconi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Damage ◽  
Cellular Response ◽  
Senile Plaques ◽  
Tg2576 Mouse ◽  
Compensatory Response ◽  
Amyloid A ◽  
Model Of Alzheimer’S Disease

Alzheimer’s disease (AD) is the most common form of dementia, characterized by progressive neurodegeneration. Pathogenetic mechanisms, triggered byβ-amyloid (Aβ) accumulation, include oxidative stress, derived from energy homeostasis deregulation and involving mitochondria and peroxisomes. We here addressed the oxidative stress status and the elicited cellular response at the onset and during the progression of Aβpathology, studying the neocortex of Tg2576 model of AD. Age-dependent changes of oxidative damage markers, antioxidant enzymes, and related transcription factors were analysed in relation to the distribution of Aβpeptide and oligomers, by a combined molecular/morphological approach. Nucleic acid oxidative damage, accompanied by defective antioxidant defences, and decreased PGC1αexpression are already detected in 3-month-old Tg2576 neurons. Conversely, PPARαis increased in these cells, with its cytoplasmic localization suggesting nongenomic, anti-inflammatory actions. At 6 months, when intracellular Aβaccumulates, PMP70 is downregulated, indicating impairment of fatty acids peroxisomal translocation and their consequent harmful accumulation. In 9-month-old Tg2576 neocortex, Aβoligomers and acrolein deposition correlate with GFAP, GPX1, and PMP70 increases, supporting a compensatory response, involving astroglial peroxisomes. At severe pathological stages, when senile plaques disrupt cortical cytoarchitecture, antioxidant capacity is gradually lost. Overall, our data suggest early therapeutic intervention in AD, also targeting peroxisomes.

scholarly journals Oxidative Stress in Patients with Alzheimer’s Disease: Effect of Extracts of Fermented Papaya Powder

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Mario Barbagallo ◽  
Francesco Marotta ◽  
Ligia J. Dominguez
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Damage ◽  
Carica Papaya ◽  
Antioxidant Systems ◽  
Oxygen Species ◽  
Degenerative Diseases ◽  
Postmortem Studies ◽  
Disease Effect

Brain tissue is particularly susceptible to oxidative stress (OS). Increased production of reactive oxygen species (ROS), reduced antioxidant systems, and decreased efficiency in repairing mechanisms have been linked to Alzheimer’s disease (AD). Postmortem studies in AD patients’ brains have shown oxidative damage markers (i.e., lipid peroxidation, protein oxidative damage, and glycoxidation). Fermented papaya (FPP, a product ofCarica papaya Linnfermentation with yeast) is a nutraceutical supplement with favorable effects on immunological, hematological, inflammatory, and OS parameters in chronic/degenerative diseases. We studied 40 patients (age 78.2 ± 1.1 years), 28 AD patients, and 12 controls. Urinary 8-OHdG was measured to assess OS. Twenty AD patients were supplemented with FPP (Immunage, 4.5 grams/day) for 6 months, while controls did not receive any treatment. At baseline, 8-OHdG was significantly higher in patients with AD versus controls (13.7 ± 1.61 ng/mL versus 1.6 ± 0.12 ng/mL,P<0.01). In AD patients FPP significantly decreased 8-OHdG (14.1 ± 1.7 ng/mL to 8.45 ± 1.1 ng/mL,P<0.01), with no significant changes in controls. AD is associated with increased OS, and FPP may be helpful to counteract excessive ROS in AD patients.

Sign in / Sign up

Export Citation Format

Share Document