scholarly journals Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents

Marine Drugs ◽  
2022 ◽  
Vol 20 (1) ◽  
pp. 75
Author(s):  
Elisabete Lima ◽  
Jorge Medeiros
Keyword(s):  
Oxidative Stress ◽  
Complex Disease ◽  
Marine Organisms ◽  
Neuroprotective Effects ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Amino Acid Tryptophan ◽  
Τ Protein ◽  
Derivatives Of ◽  
Neuron Apoptosis

The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), increases continuously demanding the urgent development of anti-Alzheimer’s agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, such as akaloids, to defend themselves. Therefore, the identification of marine natural products with neuroprotective effects is a necessity. Being that AD is not only a genetic but also an environmental complex disease, a treatment for AD remains to discover. As the major clinical indications (CI) of AD are extracellular plaques formed by β-amyloid (Aβ) protein, intracellular neurofibrillary tangles (NFTs) formed by hyper phosphorylated τ-protein, uncommon inflammatory response and neuron apoptosis and death caused by oxidative stress, alkaloids that may decrease CI, might be used against AD. Most of the alkalolids with those properties are derivatives of the amino acid tryptophan mainly with a planar indole scaffold. Certainly, alkaloids targeting more than one CI, multitarget-directed ligands (MTDL), have the potential to become a lead in AD treatment. Alkaloids to have a maximum of activity against CI, should be planar and contain halogens and amine quaternization.

scholarly journals β-Asarone Ameliorates β-Amyloid–Induced Neurotoxicity in PC12 Cells by Activating P13K/Akt/Nrf2 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Miaomiao Meng ◽  
Lijuan Zhang ◽  
Di AI ◽  
Hongyun Wu ◽  
Wei Peng
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Neuronal Damage ◽  
Cell Model ◽  
Cell Damage ◽  
Neuroprotective Effects ◽  
Akt Phosphorylation ◽  
Nrf2 Signaling Pathway ◽  
Amyloid Aβ ◽  
Β Amyloid

Accumulation of β-amyloid (Aβ) causes oxidative stress, which is the major pathological mechanism in Alzheimer’s disease (AD). β-asarone could reduce Aβ-induced oxidative stress and neuronal damage, but the molecular mechanism remains elusive. In this study, we used an Aβ-stimulated PC12 cell model to explore the neuroprotective effects and potential mechanisms of β-asarone. The results showed that β-asarone could improve cell viability and weaken cell damage and apoptosis. β-asarone could also decrease the level of ROS and MDA; increase the level of SOD, CAT, and GSH-PX; and ameliorate the mitochondrial membrane potential. Furthermore, β-asarone could promote the expression of Nrf2 and HO-1 by upregulating the level of PI3K/Akt phosphorylation. In conclusion, β-asarone could exert neuroprotective effects by modulating the P13K/Akt/Nrf2 signaling pathway. β-asarone might be a promising therapy for AD.

scholarly journals Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 985
Author(s):  
Luisa Müller ◽  
Nicole Power Guerra ◽  
Jan Stenzel ◽  
Claire Rühlmann ◽  
Tobias Lindner ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Neuroprotective Effect ◽  
Resonance Spectroscopy ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Positron Emission ◽  
Pet Ct ◽  
Amyloid Aβ ◽  
Β Amyloid

Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.

scholarly journals 9-Methylfascaplysin Is a More Potent Aβ Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 121 ◽  
Author(s):  
Qingmei Sun ◽  
Fufeng Liu ◽  
Jingcheng Sang ◽  
Miaoman Lin ◽  
Jiale Ma ◽  
...  
Keyword(s):  
Amino Acid Residues ◽  
Neuroprotective Effects ◽  
Study Results ◽  
Aβ Aggregation ◽  
Aggregation Inhibitors ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Dynamics Simulations ◽  
Aβ Oligomer

β-Amyloid (Aβ) is regarded as an important pathogenic target for Alzheimer’s disease (AD), the most prevalent neurodegenerative disease. Aβ can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Aβ aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the marine-derived alkaloid, fascaplysin, inhibits Aβ fibrillization in vitro. Moreover, the new analogue, 9-methylfascaplysin, was designed and synthesized from 5-methyltryptamine. Interestingly, 9-methylfascaplysin is a more potent inhibitor of Aβ fibril formation than fascaplysin. Incubation of 9-methylfascaplysin with Aβ directly reduced Aβ oligomer formation. Molecular dynamics simulations revealed that 9-methylfascaplysin might interact with negatively charged residues of Aβ42 with polar binding energy. Hydrogen bonds and π–π interactions between the key amino acid residues of Aβ42 and 9-methylfascaplysin were also suggested. Most importantly, compared with the typical Aβ oligomer, Aβ modified by nanomolar 9-methylfascaplysin produced less neuronal toxicity in SH-SY5Y cells. 9-Methylfascaplysin appears to be one of the most potent marine-derived compounds that produces anti-Aβ neuroprotective effects. Given previous reports that fascaplysin inhibits acetylcholinesterase and induces P-glycoprotein, the current study results suggest that fascaplysin derivatives can be developed as novel anti-AD drugs that possibly act via inhibition of Aβ aggregation along with other target mechanisms.

Mechanisms of Natural Food Dyes Curcumin on Regulation of HO-1/HO-2 and Inhibition of Aβ-Heme Compound in Alzheimer's Disease

2013 ◽  
Vol 781-784 ◽  
pp. 1148-1151 ◽  
Author(s):  
Xiong Zhang ◽  
Yang Lü ◽  
Jie Yun Sun ◽  
Yong Tang ◽  
Li Yu
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Dynamic Balance ◽  
Aging Brain ◽  
Natural Food ◽  
Key Factors ◽  
Food Dyes ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Underlying Mechanisms

More and more studies have reported that β-amyloid (Aβ)-induced oxidative stress and protein metabolism disorders along with their interactions are likely to be the key factors to the pathogenesis of Alzheimers disease (AD). Heme oxygenase (HO) is one member of stress responsive enzyme super family and is a joint of many hypothesis for AD, while oxidative stress, iron metabolism disorders and Aβ deposition are closely related with HO. Therefore, HO is expected to become a therapeutic target for AD. HO-1 and HO-2 are the main members of HO family, and keep dynamic balance. In normal aging brain tissues, the expression of HO-2 is high, and that of HO-1 is low; while in the cerebral cortex and hippocampus of AD patients, the expression of HO-1 is significantly increased. This phenomenon indicates that HO-1 has a protective effect to the neurons from the oxidative stress. Furthermore, heme and Aβ could form Aβ-heme compound, which is a peroxidase complex, which increase the oxidative damage to neurons. Recently, Curcumin has been shown cytoprotective properties by inducing HO-1 and by preventing the formation of Aβ-heme in neurons; however, the underlying mechanisms are still unclear to date. Therefore, there has been great interest in understanding the molecular mechanisms based on curcumin acts on.

Neuroprotective effects of Eriobotrya japonica against β-amyloid-induced oxidative stress and memory impairment

2011 ◽  
Vol 49 (4) ◽  
pp. 780-784 ◽  
Author(s):  
Mi-Jeong Kim ◽  
Jeongmin Lee ◽  
Ah-Reum Seong ◽  
Yoo-Hyun Lee ◽  
Yung-Jae Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Memory Impairment ◽  
Eriobotrya Japonica ◽  
Neuroprotective Effects ◽  
Β Amyloid

scholarly journals Ginsenoside Rh1 Exerts Neuroprotective Effects by Activating the PI3K/Akt Pathway in Amyloid-β Induced SH-SY5Y Cells

2021 ◽  
Vol 11 (12) ◽  
pp. 5654
Author(s):  
Miey Park ◽  
So-Hyeun Kim ◽  
Hae-Jeung Lee
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Signaling Pathways ◽  
Neurodegenerative Disorders ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Tau Proteins ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma ◽  
Β Amyloid

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of β-amyloid plaques and hyperphosphorylated tau proteins in the brain. Cell signaling pathways such as PI3K/Akt are known to play an essential role in regulating cell survival, motility, transcription, metabolism, and progression of the cell cycle. Recent studies demonstrated that the disruption of these signaling pathways in neurodegenerative disorders leads to oxidative stress and cell death. Targeting these altered signaling pathways could be considered as the therapeutic approach for neurodegenerative disorders. Ginsenoside Rh1 is known to provide beneficial effects in various diseases such as cancer, diabetes, and inflammation. In this study, human neuroblastoma SH-SY5Y cells were treated with the β-amyloid oligomers alone or in combination with ginsenoside Rh1. We observed that ginsenoside Rh1 was able to attenuate β-amyloid induced oxidative stress and cell death by activating the PI3K/Akt signaling pathway. Based on these findings, we suggest that ginsenoside Rh1 might be an efficacious therapeutic agent for AD.

scholarly journals Responsive Expression of MafF to β-Amyloid-Induced Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xiaoxuan Wang ◽  
Yu Zhang ◽  
Xinkun Wan ◽  
Chenjia Guo ◽  
Jing Cui ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Leucine Zipper ◽  
Expression Patterns ◽  
Gene Expression Omnibus ◽  
Braak Stage ◽  
Specific Expression ◽  
Glutamate Cysteine Ligase ◽  
Intrahippocampal Injection ◽  
Amyloid Aβ ◽  
Β Amyloid

The small musculoaponeurotic fibrosarcoma (sMaf) proteins MafF, MafG, and MafK are basic region leucine zipper- (bZIP-) type transcription factors and display tissue- or stimulus-specific expression patterns. As the oxidative stress reactive proteins, sMafs are implicated in various neurological disorders. In the present study, the expressions of sMafs were investigated across five databases gathering transcriptomic data from 74 Alzheimer’s disease (AD) patients and 66 controls in the Gene Expression Omnibus (GEO) database. The expression of MafF was increased in the hippocampus of AD patients, which was negatively correlated with the expression of the glutamate cysteine ligase catalytic subunit (GCLC). Furthermore, MafF was significantly increased in patients with Braak stage V-VI, compared to those with Braak stage III-IV. β-Amyloid (Aβ), a strong inducer of oxidative stress, plays a crucial role in the pathogenesis of AD. The responsive expressions of sMafs to Aβ-induced oxidative stress were studied in the APP/PS1 mouse model of AD, Aβ intrahippocampal injection rats, and several human cell lines from different tissue origins. This study revealed that only the induction of MafF was accompanied with reduction of GCLC and glutathione (GSH). MafF knockdown suppressed the increase of GSH induced by Aβ. Among sMafs, MafF is the most responsive to Aβ-induced oxidative stress and might potentiate the inhibition of antioxidation. These results provide a better understanding of sMaf modulation in AD and highlight MafF as a potential therapeutic target in AD.

scholarly journals Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg?

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1479
Author(s):  
Elena Tamagno ◽  
Michela Guglielmotto ◽  
Valeria Vasciaveo ◽  
Massimo Tabaton
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangle ◽  
Metabolic Dysfunction ◽  
Antioxidant Treatment ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Ad Alzheimer’S Disease ◽  
Important Therapeutic Target

The pathogenesis of Alzheimer’s disease involves β amyloid (Aβ) accumulation known to induce synaptic dysfunction and neurodegeneration. The brain’s vulnerability to oxidative stress (OS) is considered a crucial detrimental factor in Alzheimer’s disease. OS and Aβ are linked to each other because Aβ induces OS, and OS increases the Aβ deposition. Thus, the answer to the question “which comes first: the chicken or the egg?” remains extremely difficult. In any case, the evidence for the primary occurrence of oxidative stress in AD is attractive. Thus, evidence indicates that a long period of gradual oxidative damage accumulation precedes and results in the appearance of clinical and pathological AD symptoms, including Aβ deposition, neurofibrillary tangle formation, metabolic dysfunction, and cognitive decline. Moreover, oxidative stress plays a crucial role in the pathogenesis of many risk factors for AD. Alzheimer’s disease begins many years before its symptoms, and antioxidant treatment can be an important therapeutic target for attacking the disease.

Neurochemical Aspects of Alzheimer’s Disease and Movement Disturbances: A Theory of β-Amyloid and τ-Protein

2018 ◽  
Vol 33 (8) ◽  
pp. 535-540 ◽  
Author(s):  
Auda Fares ◽  
Dieter Borrmann
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Large Body ◽  
Motor Dysfunction ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Τ Protein ◽  
The Relationship

The pathologic and molecular substrate of people diagnosed with cognitive deficits and movement disturbance may not occur exclusively in the context of a brain region, but it may be expressed in another part of body such as muscle. A large body of research has demonstrated that slow motor performance is associated with cognitive impairment in elderly people. The interdependence between motor dysfunction and cognition decline is still not fully understood. Although several factors have been suggested to give a plausible explanation, β-amyloid (Aβ) and τ-protein aggregation is a common feature of a number of neurodegenerative disorders which are characterized by both motor and cognitive impairment, and it is assumed that the aggregation process plays a central role in the pathogenesis of cognitive impairment and motor dysfunction in Alzheimer’s disease. The purpose of the present review is to provide an overview of the available evidence that can help to better elucidate the pathophysiological mechanisms underlying the relationship between cognitive and movement disturbances by focusing on Aβ and τ-protein.

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