Adiponectin is Protective against Oxidative Stress Induced Cytotoxicity in Amyloid-Beta Neurotoxicity

Mango peels are usually discarded as waste; however, they contain phytochemicals and could provide functional properties to food and promote human health. This study aimed to determine the optimal lactic acid bacteria for fermentation of mango peel and evaluate the effect of mango peel on neuronal protection in Neuron-2A cells against amyloid beta (Aβ) treatment (50 μM). Mango peel can be fermented by different lactic acid bacteria species. Lactobacillus acidophilus (BCRC14079)-fermented mango peel produced the highest concentration of lactic acid bacteria (exceeding 108 CFU/mL). Mango peel and fermented mango peel extracts upregulated brain-derived neurotrophic factor (BDNF) expression for 1.74-fold in Neuron-2A cells. Furthermore, mango peel fermented products attenuated oxidative stress in Aβ-treated neural cells by 27%. Extracts of L. acidophilus (BCRC14079)-fermented mango peel treatment decreased Aβ accumulation and attenuated the increase of subG1 caused by Aβ induction in Neuron-2A cells. In conclusion, L. acidophilus (BCRC14079)-fermented mango peel acts as a novel neuronal protective product by inhibiting oxidative stress and increasing BDNF expression in neural cells.

Download Full-text

The Role of Oxidative Stress-Induced Epigenetic Alterations in Amyloid-βProduction in Alzheimer’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/604658 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 50

Author(s):

Li Zuo ◽

Benjamin T. Hemmelgarn ◽

Chia-Chen Chuang ◽

Thomas M. Best

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Beta ◽

Treatment Options ◽

Memory Loss ◽

The United States ◽

Traditional Medicines ◽

Progressive Neurodegeneration ◽

Antioxidant Supplements

An increasing number of studies have proposed a strong correlation between reactive oxygen species (ROS)-induced oxidative stress (OS) and the pathogenesis of Alzheimer’s disease (AD). With over five million people diagnosed in the United States alone, AD is the most common type of dementia worldwide. AD includes progressive neurodegeneration, followed by memory loss and reduced cognitive ability. Characterized by the formation of amyloid-beta (Aβ) plaques as a hallmark, the connection between ROS and AD is compelling. Analyzing the ROS response of essential proteins in the amyloidogenic pathway, such as amyloid-beta precursor protein (APP) and beta-secretase (BACE1), along with influential signaling programs of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinase (JNK), has helped visualize the path between OS and Aβoverproduction. In this review, attention will be paid to significant advances in the area of OS, epigenetics, and their influence on Aβplaque assembly. Additionally, we aim to discuss available treatment options for AD that include antioxidant supplements, Asian traditional medicines, metal-protein-attenuating compounds, and histone modifying inhibitors.

Download Full-text

A Bifunctional Anti-Amyloid Blocks Oxidative Stress and the Accumulation of Intraneuronal Amyloid-Beta

Molecules ◽

10.3390/molecules23082010 ◽

2018 ◽

Vol 23 (8) ◽

pp. 2010 ◽

Cited By ~ 7

Author(s):

Silvia Hilt ◽

Robin Altman ◽

Tamás Kálai ◽

Izumi Maezawa ◽

Qizhi Gong ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Line ◽

Small Molecule ◽

Amyloid Beta ◽

Disease Process ◽

Neuronal Cell ◽

Super Resolution ◽

Microscopy Imaging ◽

Neuronal Cell Line ◽

Intimate Link

There is growing recognition regarding the role of intracellular amyloid beta (Aβ) in the Alzheimer’s disease process, which has been linked with aberrant signaling and the disruption of protein degradation mechanisms. Most notably, intraneuronal Aβ likely underlies the oxidative stress and mitochondrial dysfunction that have been identified as key elements of disease progression. In this study, we employed fluorescence imaging to explore the ability of a bifunctional small molecule to reduce aggregates of intracellular Aβ and attenuate oxidative stress. Structurally, this small molecule is comprised of a nitroxide spin label linked to an amyloidophilic fluorene and is known as spin-labeled fluorene (SLF). The effect of the SLF on intracellular Aβ accumulation and oxidative stress was measured in MC65 cells, a human neuronal cell line with inducible expression of the amyloid precursor protein and in the N2a neuronal cell line treated with exogenous Aβ. Super-resolution microscopy imaging showed SLF decreases the accumulation of intracellular Aβ. Confocal microscopy imaging of MC65 cells treated with a reactive oxygen species (ROS)-sensitive dye demonstrated SLF significantly reduces the intracellular Aβ-induced ROS signal. In order to determine the contributions of the separate SLF moieties to these protective activities, experiments were also carried out on cells with nitroxides lacking the Aβ targeting domain or fluorene derivatives lacking the nitroxide functionality. The findings support a synergistic effect of SLF in counteracting both the conformational toxicity of both endogenous and exogenous Aβ, its promotion of ROS, and Aβ metabolism. Furthermore, these studies demonstrate an intimate link between ROS production and Aβ oligomer formation.

Download Full-text

Chronic Administration of Scopolamine Increased GSK3βP9, Beta Secretase, Amyloid Beta, and Oxidative Stress in the Hippocampus of Wistar Rats

Molecular Neurobiology ◽

10.1007/s12035-020-02009-x ◽

2020 ◽

Vol 57 (9) ◽

pp. 3979-3988 ◽

Cited By ~ 2

Author(s):

Maricarmen Hernández-Rodríguez ◽

Ivonne Maciel Arciniega-Martínez ◽

Iohanan Daniel García-Marín ◽

José Correa-Basurto ◽

Martha Cecilia Rosales-Hernández

Keyword(s):

Oxidative Stress ◽

Amyloid Beta ◽

Wistar Rats ◽

Chronic Administration ◽

Beta Secretase ◽

And Oxidative Stress

Download Full-text

Amyloid Beta-Peptide Increases BACE1 Translation through the Phosphorylation of the Eukaryotic Initiation Factor-2α

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/2739459 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Pol Picón-Pagès ◽

Daniela A. Gutiérrez ◽

Alejandro Barranco-Almohalla ◽

Giulia Crepin ◽

Marta Tajes ◽

...

Keyword(s):

Oxidative Stress ◽

Free Radicals ◽

Western Blot ◽

Amyloid Beta ◽

Initiation Factor ◽

Amyloid Beta Peptide ◽

Braak Stage ◽

Eukaryotic Initiation Factor ◽

Bace1 Expression ◽

Beta Peptide

Alzheimer’s disease (AD) is tightly linked to oxidative stress since amyloid beta-peptide (Aβ) aggregates generate free radicals. Moreover, the aggregation of Aβ is increased by oxidative stress, and the neurotoxicity induced by the oligomers and fibrils is in part mediated by free radicals. Interestingly, it has been reported that oxidative stress can also induce BACE1 transcription and expression. BACE1 is the key enzyme in the cleavage of the amyloid precursor protein to produce Aβ, and the expression of this enzyme has been previously shown to be enhanced in the brains of Alzheimer’s patients. Here, we have found that BACE1 expression is increased in the hippocampi from AD patients at both the early (Braak stage II) and late (Braak stage VI) stages of the disease as studied by immunohistochemistry and western blot. To address the role of Aβ and oxidative stress in the regulation of BACE1 expression, we have analyzed the effect of subtoxic concentrations of Aβ oligomers (0.25 μM) and H2O2 (10 mM) on a human neuroblastoma cell line. Firstly, our results show that Aβ oligomers and H2O2 induce an increase of BACE1 mRNA as we studied by qPCR. Regarding BACE1 translation, it is dependent on the phosphorylation of the eukaryotic initiation factor 2α (eIF2α), since BACE1 mRNA bears a 5′UTR that avoids its translation under basal conditions. BACE1 5′UTR contains four upstream initiating codons (uAUGs), and its translation is activated when eIF2α is phosphorylated. Consistently, we have obtained that Aβ oligomers and H2O2 increase the levels of BACE1 and p-eIF2α assayed by western blot and confocal microscopy. Our results suggest that Aβ oligomers increase BACE1 translation by phosphorylating eIF2α in a process that involves oxidative stress and conforms a pathophysiological loop, where the Aβ once aggregated favors its own production continuously by the increase in BACE1 expression as observed in AD patients.

Download Full-text

Caniferolide A, a Macrolide from Streptomyces caniferus, Attenuates Neuroinflammation, Oxidative Stress, Amyloid-Beta, and Tau Pathology in Vitro

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.8b01090 ◽

2019 ◽

Vol 16 (4) ◽

pp. 1456-1466 ◽

Cited By ~ 5

Author(s):

Rebeca Alvariño ◽

Eva Alonso ◽

Rodney Lacret ◽

Daniel Oves-Costales ◽

Olga Genilloud ◽

...

Keyword(s):

Oxidative Stress ◽

Amyloid Beta ◽

Tau Pathology

Download Full-text

Simvastatin improves cerebrovascular function and counters soluble amyloid-beta, inflammation and oxidative stress in aged APP mice

Neurobiology of Disease ◽

10.1016/j.nbd.2009.06.003 ◽

2009 ◽

Vol 35 (3) ◽

pp. 406-414 ◽

Cited By ~ 78

Author(s):

Xin-Kang Tong ◽

Nektaria Nicolakakis ◽

Priscilla Fernandes ◽

Brice Ongali ◽

Jonathan Brouillette ◽

...

Keyword(s):

Oxidative Stress ◽

Amyloid Beta ◽

Cerebrovascular Function ◽

And Oxidative Stress

Download Full-text

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

Current Psychopharmacologye ◽

10.2174/2211556009666191231155927 ◽

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.

Download Full-text

Telomerase increasing compound protects hippocampal neurons from amyloid beta toxicity by enhancing the expression of neurotrophins and plasticity related genes

Scientific Reports ◽

10.1038/s41598-019-54741-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Natalie Baruch-Eliyahu ◽

Vladislav Rud ◽

Alex Braiman ◽

Esther Priel

Keyword(s):

Oxidative Stress ◽

Amyloid Beta ◽

Neurotrophic Factors ◽

Hippocampal Neurons ◽

Neuroprotective Effect ◽

Adult Brain ◽

Beta Catenin ◽

Adult Mice ◽

Hippocampal Cell Culture ◽

Neuronal Degradation

AbstractThe telomerase reverse transcriptase protein, TERT, is expressed in the adult brain and its exogenic expression protects neurons from oxidative stress and from the cytotoxicity of amyloid beta (Aβ). We previously showed that telomerase increasing compounds (AGS) protected neurons from oxidative stress. Therefore, we suggest that increasing TERT by AGS may protect neurons from the Aβ-induced neurotoxicity by influencing genes and factors that participate in neuronal survival and plasticity. Here we used a primary hippocampal cell culture exposed to aggregated Aβ and hippocampi from adult mice. AGS treatment transiently increased TERT gene expression in hippocampal primary cell cultures in the presence or absence of Aβ and protected neurons from Aβ induced neuronal degradation. An increase in the expression of Growth associated protein 43 (GAP43), and Feminizing locus on X-3 genes (NeuN), in the presence or absence of Aβ, and Synaptophysin (SYP) in the presence of Aβ was observed. GAP43, NeuN, SYP, Neurotrophic factors (NGF, BDNF), beta-catenin and cyclin-D1 expression were increased in the hippocampus of AGS treated mice. This data suggests that increasing TERT by pharmaceutical compounds partially exerts its neuroprotective effect by enhancing the expression of neurotrophic factors and neuronal plasticity genes in a mechanism that involved Wnt/beta-catenin pathway.

Download Full-text