scholarly journals Supplementation with Curcuma longa Reverses Neurotoxic and Behavioral Damage in Models of Alzheimer’s Disease: A Systematic Review

2019 ◽  
Vol 17 (5) ◽  
pp. 406-421 ◽  
Author(s):  
Ianara Mendonça da Costa ◽  
Marco Aurelio de Moura Freire ◽  
José Rodolfo Lopes de Paiva Cavalcanti ◽  
Dayane Pessoa de Araújo ◽  
Bianca Norrara ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Curcuma Longa ◽  
Senile Plaques ◽  
Experimental Models ◽  
Cochrane Library

Background: The formation of senile plaques and neurofibrillary tangles of the tau protein are the main pathological mechanism of Alzheimer’s disease (AD). Current therapies for AD offer discrete benefits to the clinical symptoms and do not prevent the continuing degeneration of neuronal cells. Therefore, novel therapeutic strategies have long been investigated, where curcumin (Curcuma longa) has shown some properties that can prevent the deleterious processes involved in neurodegenerative diseases. Objective: The aim of the present work is to review studies that addressed the effects of curcumin in experimental models (in vivo and in vitro) for AD. Method: This study is a systematic review conducted between January and June 2017, in which a consultation of scientific articles from indexed periodicals was carried out in Science Direct, United States National Library of Medicine (PubMed), Cochrane Library and Scielo databases, using the following descriptors: “Curcuma longa”, “Curcumin” and “Alzheimer’s disease”. Results: A total of 32 studies were analyzed, which indicated that curcumin supplementation reverses neurotoxic and behavioral damages in both in vivo and in vitro models of AD. Conclusion: The administration of curcumin in experimental models seems to be a promising approach in AD, even though it is suggested that additional studies must be conducted using distinct doses and through other routes of administration.

scholarly journals Resveratrol in Alzheimer's disease: a review of pathophysiology and therapeutic potential

2020 ◽  
Vol 78 (8) ◽  
pp. 501-511 ◽  
Author(s):  
Júlia Canto e SOUSA ◽  
Ana Carolina Fauaze SANTANA ◽  
Gabriela Jesus Prado MAGALHÃES
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Senile Plaques ◽  
Cochrane Library ◽  
Original Research ◽  
Protective Effects

ABSTRACT Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive and irreversible loss of cognitive function. The presence of senile plaques is one of the pathological markers of the disease and is associated with the onset of neuroinflammatory mechanisms. The exact pathophysiology of AD has not been completely understood, and there are no curative therapies yet. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol that is noted for its antioxidant and anti-inflammatory properties. Objective: To review the role of resveratrol in the pathophysiological aspects of AD. Methods: This study carried out a literature review using PubMed/Medline, Virtual Health Library (VHL), Web of Sciences, SCOPUS and the Cochrane Library databases. Original research articles, describing both in vitro and in vivo experiments, published between 2008 and 2018, were included. Results: We identified 667 articles, of which 619 were excluded because they were repeated or did not follow the inclusion criteria. The present study includes the remaining 48 articles. Discussion: Resveratrol demonstrates beneficial and protective effects in AD models and seems to provide a promising therapeutic alternative. Conclusion: Although resveratrol appears to mitigate some pathophysiological aspects of AD, further studies are needed to prove the safety and efficacy of this compound in humans.

scholarly journals Red Ginseng Attenuates Aβ-Induced Mitochondrial Dysfunction and Aβ-mediated Pathology in an Animal Model of Alzheimer’s Disease

2019 ◽  
Vol 20 (12) ◽  
pp. 3030 ◽  
Author(s):  
Soo Jung Shin ◽  
Seong Gak Jeon ◽  
Jin-il Kim ◽  
Yu-on Jeong ◽  
Sujin Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Formation ◽  
Experimental Models ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Red Ginseng ◽  
Model Of Alzheimer’S Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by neurodegeneration and cognitive deficits. Amyloid beta (Aβ) peptide is known to be a major cause of AD pathogenesis. However, recent studies have clarified that mitochondrial deficiency is also a mediator or trigger for AD development. Interestingly, red ginseng (RG) has been demonstrated to have beneficial effects on AD pathology. However, there is no evidence showing whether RG extract (RGE) can inhibit the mitochondrial deficit-mediated pathology in the experimental models of AD. The effects of RGE on Aβ-mediated mitochondrial deficiency were investigated in both HT22 mouse hippocampal neuronal cells and the brains of 5XFAD Aβ-overexpressing transgenic mice. To examine whether RGE can affect mitochondria-related pathology, we used immunohistostaining to study the effects of RGE on Aβ accumulation, neuroinflammation, neurodegeneration, and impaired adult hippocampal neurogenesis in hippocampal formation of 5XFAD mice. In vitro and in vivo findings indicated that RGE significantly improves Aβ-induced mitochondrial pathology. In addition, RGE significantly ameliorated AD-related pathology, such as Aβ deposition, gliosis, and neuronal loss, and deficits in adult hippocampal neurogenesis in brains with AD. Our results suggest that RGE may be a mitochondria-targeting agent for the treatment of AD.

To rectify Alzheimer's disease etiology, excessive mitochondrial division might be stopped or mitophagy might be promoted

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Senile Plaques ◽  
Mitochondrial Division ◽  
Disease Etiology ◽  
Abnormal Mitochondria ◽  
Unifying Principles

In both in vitro and in vivo Alzheimer's disease (AD) models, mitochondrial dysfunction is a crucial feature that limits neuronal activity and results in A and phosphorylated Tau toxicity. To rectify AD etiology, excessive mitochondrial division might be stopped or mitophagy might be promoted. However, there are still unexplained mysteries surrounding the formation of senile plaques and NFTs, and the pathophysiology of Alzheimer's disease lacks fundamental unifying principles. Some scientists believe A toxicity and Tau toxicity are upstream processes in mitochondrial dysfunction, while others feel it is a downstream chain of events involving abnormal mitochondria. There are several mitophagy mechanisms for the clearance of dead mitochondria in PINK1 signaling; some are regulated by Parkin, while others are not. Drp1, Mfn1/2, PINK1, or Parkin, according to some researchers, have no role in mitophagy cleaning dysfunctional mitochondria; so, additional study is needed to solve the puzzle of mitophagy signaling pathways for clearing dead mitochondria and conserving high-quality mitochondria. Therapeutic techniques targeting mitophagy activity might be useful in reversing AD etiology.

scholarly journals Apolipoprotein E forms stable complexes with recombinant Alzheimer's disease β-amyloid precursor protein

1997 ◽  
Vol 325 (1) ◽  
pp. 169-175 ◽  
Author(s):  
Cristina HAAS ◽  
Pilar CAZORLA ◽  
Carlos DE MIGUEL ◽  
Fernando VALDIVIESO ◽  
Jesús VÁZQUEZ
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Senile Plaques ◽  
Precursor Protein ◽  
Amyloid Peptide ◽  
Reducing Conditions ◽  
Β Amyloid

Apolipoprotein E (apoE), a protein genetically linked to the incidence of Alzheimer's disease, forms SDS-stable complexes in vitro with β-amyloid peptide (Aβ), the primary component of senile plaques. In the present study, we investigated whether apoE was able to bind full-length Aβ precursor protein (APP). Using a maltose-binding-protein–APP fusion protein and human very-low-density lipoprotein (VLDL), we detected an interaction of apoE with APP that was inhibited by Aβ or anti-apoE antibody. Saturation-binding experiments indicated a single binding equilibrium with an apparent 1:1 stoichiometry and a dissociation constant of 15 nM. An interaction was also observed using apoE from cerebrospinal fluid or delipidated VLDL, as well as recombinant apoE. APP·apoE complexes were SDS-stable, and their formation was not inhibited by reducing conditions; however, they were dissociated by SDS under reducing conditions. ApoE·APP complexes formed high-molecular-mass aggregates, and competition experiments suggested that amino acids 14–23 of Aβ are responsible for complex-formation. Finally, no differences were found when studying the interaction of APP with apoE3 or apoE4. Taken together, our results demonstrate that apoE may form stable complexes with the Aβ moiety of APP with characteristics similar to those of complexes formed with isolated Aβ, and suggest the intriguing possibility that apoE–APP interactions may be pathologically relevant in vivo.

scholarly journals Neurovascular function in Alzheimer's disease patients and experimental models

2011 ◽  
Vol 31 (6) ◽  
pp. 1354-1370 ◽  
Author(s):  
Nektaria Nicolakakis ◽  
Edith Hamel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Experimental Models ◽  
Model Systems ◽  
In Vivo Model ◽  
Vessel Structure ◽  
Integral Element ◽  
Neurovascular Dysfunction

The ability of the brain to locally augment glucose delivery and blood flow during neuronal activation, termed neurometabolic and neurovascular coupling, respectively, is compromised in Alzheimer's disease (AD). Since perfusion deficits may hasten clinical deterioration and have been correlated with negative treatment outcome, strategies to improve the cerebral circulation should form an integral element of AD therapeutic efforts. These efforts have yielded several experimental models, some of which constitute AD models proper, others which specifically recapture the AD cerebrovascular pathology, characterized by anatomical alterations in brain vessel structure, as well as molecular changes within vascular smooth muscle cells and endothelial cells forming the blood– brain barrier. The following paper will present the elements of AD neurovascular dysfunction and review the in vitro and in vivo model systems that have served to deepen our understanding of it. It will also critically evaluate selected groups of compounds, the FDA-approved cholinesterase inhibitors and thiazolidinediones, for their ability to correct neurovascular dysfunction in AD patients and models. These and several others are emerging as compounds with pleiotropic actions that may positively impact dysfunctional cerebrovascular, glial, and neuronal networks in AD.

scholarly journals Deconstructing Alzheimer’s Disease: How to Bridge the Gap between Experimental Models and the Human Pathology?

2021 ◽  
Vol 22 (16) ◽  
pp. 8769
Author(s):  
Anaïs Vignon ◽  
Lucie Salvador-Prince ◽  
Sylvain Lehmann ◽  
Véronique Perrier ◽  
Joan Torrent
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Experimental Models ◽  
Tau Proteins ◽  
Human Pathology ◽  
Set Up

Discovered more than a century ago, Alzheimer’s disease (AD) is not only still present in our societies but has also become the most common dementia, with 50 million people worldwide affected by the disease. This number is expected to double in the next generation, and no cure is currently available to slow down or stop the disease progression. Recently, some advances were made due to the approval of the aducanumab treatment by the American Food and Drug Administration. The etiology of this human-specific disease remains poorly understood, and the mechanisms of its development have not been completely clarified. Several hypotheses concerning the molecular mechanisms of AD have been proposed, but the existing studies focus primarily on the two main markers of the disease: the amyloid β peptides, whose aggregation in the brain generates amyloid plaques, and the abnormally phosphorylated tau proteins, which are responsible for neurofibrillary tangles. These protein aggregates induce neuroinflammation and neurodegeneration, which, in turn, lead to cognitive and behavioral deficits. The challenge is, therefore, to create models that best reproduce this pathology. This review aims at gathering the different existing AD models developed in vitro, in cellulo, and in vivo. Many models have already been set up, but it is necessary to identify the most relevant ones for our investigations. The purpose of the review is to help researchers to identify the most pertinent disease models, from the most often used to the most recently generated and from simple to complex, explaining their specificities and giving concrete examples.

scholarly journals Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

2020 ◽  
Vol 21 (6) ◽  
pp. 1975 ◽  
Author(s):  
Eirini Chainoglou ◽  
Dimitra Hadjipavlou-Litina
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Specific Activity ◽  
Curcuma Longa ◽  
Amyloid Β ◽  
Hydroxyl Group ◽  
Amyloid Β Peptide ◽  
Curcumin Analogues

Worldwide, Alzheimer’s disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly preventing or treating AD. During the last decade, the scientific community has focused their research on the optimization of therapeutic properties and on the improvement of pharmacokinetic properties of curcumin. This review summarizes bibliographical data from 2009 to 2019 on curcumin analogues, derivatives, and hybrids, as well as their therapeutic, preventic, and diagnostic applications in AD. Recent advances in the field have revealed that the phenolic hydroxyl group could contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seem to contribute to the suppression of amyloid-β peptide (Aβ42) and to the suppression of amyloid precursor protein (APP) andhydrophobic interactions have also revealed a growing role. Furthermore, flexible moieties, at the linker, are crucial for the inhibition of Aβ aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The promising role of curcumin-based compounds in diagnostic imaging is highlighted. The keto-enol tautomerism seems to be a novel modification for the design of amyloid-binding agents. Molecular docking results, (Q)SAR, as well as in vitro and in vivo tests highlight the structures and chemical moieties that are correlated with specific activity. As a result, the knowledge gained from the existing research should lead to the design and synthesis ofinnovative and multitargetedcurcumin analogues, derivatives, or curcumin hybrids, which would be very useful drug and tools in medicine for both diagnosis and treatment of AD.

scholarly journals Palmitoylethanolamide Dampens Reactive Astrogliosis and Improves Neuronal Trophic Support in a Triple Transgenic Model of Alzheimer’s Disease: In Vitro and In Vivo Evidence

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Maria Rosanna Bronzuoli ◽  
Roberta Facchinetti ◽  
Luca Steardo ◽  
Adele Romano ◽  
Claudia Stecca ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Neuronal Loss ◽  
Adjunct Treatment ◽  
Reactive Astrogliosis ◽  
Model Of Alzheimer’S Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder responsible for the majority of dementia cases in elderly people. It is widely accepted that the main hallmarks of AD are not only senile plaques and neurofibrillary tangles but also reactive astrogliosis, which often precedes detrimental deposits and neuronal atrophy. Such phenomenon facilitates the regeneration of neural networks; however, under some circumstances, like in AD, reactive astrogliosis is detrimental, depriving neurons of the homeostatic support, thus contributing to neuronal loss. We investigated the presence of reactive astrogliosis in 3×Tg-AD mice and the effects of palmitoylethanolamide (PEA), a well-documented anti-inflammatory molecule, by in vitro and in vivo studies. In vitro results revealed a basal reactive state in primary cortical 3×Tg-AD-derived astrocytes and the ability of PEA to counteract such phenomenon and improve viability of 3×Tg-AD-derived neurons. In vivo observations, performed using ultramicronized- (um-) PEA, a formulation endowed with best bioavailability, confirmed the efficacy of this compound. Moreover, the schedule of treatment, mimicking the clinic use (chronic daily administration), revealed its beneficial pharmacological properties in dampening reactive astrogliosis and promoting the glial neurosupportive function. Collectively, our results encourage further investigation on PEA effects, suggesting it as an alternative or adjunct treatment approach for innovative AD therapy.

scholarly journals Bojungikgi-Tang, a Traditional Herbal Formula, Exerts Neuroprotective Effects and Ameliorates Memory Impairments in Alzheimer’s Disease-Like Experimental Models

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1952 ◽  
Author(s):  
Hye-Sun Lim ◽  
Yu Kim ◽  
Eunjin Sohn ◽  
Jiyeon Yoon ◽  
Bu-Yeo Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant Activity ◽  
Experimental Models ◽  
Herbal Formula ◽  
Neuroprotective Effects ◽  
Free System ◽  
Aβ Aggregation

Bojungikgi-tang (BJIGT; Bu Zhong Yi Qi Tang in China, Hochuekkito in Japan) is a traditional Oriental herbal formula comprised of eight medicinal herbs that has long been used for the treatment of digestive disorders. A recent clinical study from South Korea reported that BJIGT-gamibang administration may be effective in treating dementia. We aimed to establish scientific evidence for the anti-dementia effects of BJIGT using in vitro and in vivo experimental models. We measured amyloid- β (Aβ) aggregation, β-secretase (BACE), and antioxidant activity in a cell free system. Neuroprotective effects were assessed using CCK-8. Imprinting control region (ICR) mice were divided into the following six groups: Normal control, Aβ-injected, Aβ-injection + oral BJIGT gavage (200, 400, or 800 mg/kg/day), and Aβ-injection + oral morin administration (10 mg/kg/day). Subsequently, behavioral evaluations were conducted and brain samples were collected from all the animals and assessed. BJIGT enhanced inhibition of Aβ aggregation and BACE activity in vivo, as well as antioxidant activity in in vitro, cell-free systems. BJIGT also exerted neuroprotective effects in a hydroperoxide (H2O2)-induced damaged HT22 hippocampal cell line model. In addition, BJIGT administration significantly ameliorated cognitive impairments in Aβ-injected mice, as assessed by the passive avoidance and Y-maze tests. Furthermore, BJIGT treatment suppressed Aβ aggregation and expression, as well as expression of Aβ, NeuN, and brain-derived neurotrophic factor (BDNF) in the hippocampi of Aβ-injected mice. Overall, our results demonstrate that, with further testing in clinical populations, BJIGT may have great utility for the treatment of dementia and especially Alzheimer’s disease.

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