Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

2020 ◽  
Vol 17 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Dubravka S. Strac ◽  
Marcela Konjevod ◽  
Matea N. Perkovic ◽  
Lucija Tudor ◽  
Gordana N. Erjavec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Comprehensive Overview ◽  
Brain Functions ◽  
Specific Effects ◽  
And Behavior

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

Curcuminoids and Novel Opportunities for the Treatment of Alzheimer's Disease: Which Molecules are Actually Effective?

2019 ◽  
Vol 12 (1) ◽  
pp. 12-26 ◽  
Author(s):  
Alexander V. Zholos ◽  
Olesia F. Moroz ◽  
Maksim V. Storozhuk
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Animal Models ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Preclinical Studies ◽  
In Vitro Experiments ◽  
Beneficial Effects

Background:Millions of people worldwide are suffering from Alzheimer's disease (AD), and there are only symptomatic treatments available for this disease. Thus, there is a great need to identify drugs capable of arresting or reversing AD. Constituents of the spice turmeric, in particular, curcuminoids, seem to be very promising, as evident from in vitro experiments and tests using animal models of AD. However, most of the clinical trials did not reveal any beneficial effects of curcuminoids in the treatment of AD. These controversies, including conflicting results of clinical trials, are thought to be related to bioavailability of curcuminoids, which is low unless it is enhanced by developing a special formulation. However, there is growing evidence suggesting that other reasons may be of even greater importance, but these avenues are less explored.Objective:Review relevant literature, and analyze potential reasons for the controversial results.Methodology:Recent in vitro and preclinical studies; clinical trials (without a limiting period) were searched in PubMed and Google Scholar.Results:While recent in vitro and preclinical studies confirm the therapeutic potential of curcuminoids in the treatment of AD and cognitive dysfunctions, results of corresponding clinical trials remain rather controversial.Conclusion:The controversial results obtained in the clinical trials may be in part due to particularities of the curcuminoid formulations other than bioavailability. Namely, it seems likely that the various formulations differ in terms of their minor turmeric constituent(s). We hypothesize that these distinctions may be of key importance for efficacy of the particular formulation in clinical trials. A testable approach addressing this hypothesis is suggested.

Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cells (Admscs) and/or Taurine in Aluminum Chloride-Induced Alzheimer's Disease Rat Model

2021 ◽  
Author(s):  
Mohamed Hosney ◽  
Alaa Sakraan ◽  
Aman Asaad ◽  
Mervat El-Deftar ◽  
Emad Elzayat
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Brain Homogenate ◽  
Oxidative Stress Marker

Abstract Alzheimer's disease (AD) is the most prevalent type of dementia characterized by its progression, neurobehavioral and neuro-pathological characteristics, leading to a diverse neuronal loss. Adipose-derived mesenchymal stem cells (ADMSCs) have previously proved potential role in preventing the pathogenesis of several neurodegenerative disorders, so regarded as a promising new approach for AD regenerative therapy. Taurine was found to enhance stem cell activation and propagation yielding a higher concentration of neural progenitors and stem cells, and aid to lessen the number of activated microglia leading to down-regulated inflammation in vitro. The present study aimed to investigate the possible therapeutic potential of ADMSCs and/or taurine in treating AD rat model. It was planned to include three successive phases; induction, withdrawal, and therapeutic phases. Fifty male Wistar rats were divided into 2 main groups: control (C) group and AD model group. Behavioral changes, as manifested by the T-Maze experiment, had been recorded. β-amyloid levels had been measured in brain homogenate and serum by ELISA. Oxidative stress marker (MDA), and anti-oxidant enzymes activity (SOD, GSH, and CAT) in brain, as well as serum acetylcholine esterase activity were spectrophotometrically determined. Pro-apoptotic (p53 and Bax) and anti-apoptotic (Bcl2) gene expression in brain were evaluated using RT-qPCR. The histopathological alterations in brain tissues were also observed. The present study proved the potential therapeutic ability of ADMSCs and/or taurine in alleviating the adverse pathological changes induced by AlCl3 in AD rat model at both physiological and molecular levels.

scholarly journals The Therapeutic Potential of Berberis darwinii Stem-Bark: Quantification of Berberine and In Vitro Evidence for Alzheimer's Disease Therapy

2011 ◽  
Vol 6 (8) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Solomon Habtemariam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Charles Darwin ◽  
Potent Inhibitor ◽  
Methanolic Extract ◽  
Therapeutic Potential ◽  
Stem Bark ◽  
Acetylcholinesterase Inhibition ◽  
Disease Therapy

Berberis darwinii is native to South America but has been widely distributed in Europe and other continents following its discovery by Charles Darwin. Herewith, the therapeutic potential of stem-bark of the plant for treating Alzheimer's disease was studied using an in vitro acetylcholinesterase inhibition assay. It was found that the methanolic extract of the stem-bark was a potent inhibitor of the enzyme with an IC50 value of 1.23 ± 0.05 μg/mL. An HPLC-based berberine quantification study revealed an astonishing 38% yield of the dried methanolic extract.

scholarly journals The Therapeutic Potential of Rosemary (Rosmarinus officinalis) Diterpenes for Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Solomon Habtemariam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Rosmarinus Officinalis ◽  
Brain Inflammation ◽  
Important Species

Rosemary (Rosmarinus officinalisL.) is one of the most economically important species of the family Lamiaceae. Native to the Mediterranean region, the plant is now widely distributed all over the world mainly due to its culinary, medicinal, and commercial uses including in the fragrance and food industries. Among the most important group of compounds isolated from the plant are the abietane-type phenolic diterpenes that account for most of the antioxidant and many pharmacological activities of the plant. Rosemary diterpenes have also been shown in recent years to inhibit neuronal cell death induced by a variety of agents bothin vitroandin vivo. The therapeutic potential of these compounds for Alzheimer’s disease (AD) is reviewed in this communication by giving special attention to the chemistry of the compounds along with the various pharmacological targets of the disease. The multifunctional nature of the compounds from the general antioxidant-mediated neuronal protection to other specific mechanisms including brain inflammation and amyloid beta (Aβ) formation, polymerisation, and pathologies is discussed.

scholarly journals Therapeutic Potential Of Multifunctional Derivatives Of Cholinesterase Inhibitors

2020 ◽  
Vol 19 ◽  
Author(s):  
Maja Przybyłowska ◽  
Krystyna Dzierzbicka ◽  
Szymon Kowalski ◽  
Klaudia Chmielewska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Amyloid Plaque ◽  
Β Amyloid ◽  
Derivatives Of ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

: The aim of this work is review of tacrine analogues from the last three years, which were not included in the latest review work, donepezil and galantamine hybrids from 2015 and rivastigmine derivatives from 2014. In this account we summarize the efforts toward the development and characterization of non-toxic inhibitors of cholinesterases based on mentioned drugs with various interesting additional properties such as antioxidant, decreasing β-amyloid plaque aggregation, nitric oxide production, pro-inflammatory cytokines release, monoamine oxidase-B activity, cytotoxicity and oxidative stress in vitro and in animal model that classify these hybrids as potential multifunctional therapeutic agents for Alzheimer’s disease. Moreover, herein, we have described the cholinergic hypothesis, mechanisms of neurodegeneration and current pharmacotherapy of Alzheimer’s disease which is based on the restoration of cholinergic function through blocking enzymes that break down acetylcholine.

scholarly journals β-hydroxybutyrate Impedes the Progression of Alzheimer’s Disease and Atherosclerosis in ApoE-Deficient Mice

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 471 ◽  
Author(s):  
Manigandan Krishnan ◽  
Jong Su Hwang ◽  
Mikyung Kim ◽  
Yun Jin Kim ◽  
Ji Hae Seo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Density Lipoprotein ◽  
In Vitro Study ◽  
Substantia Nigra Pars Compacta ◽  
Apo E ◽  
The Brain ◽  
Deficient Mice

β-hydroxybutyrate (β-OHB) has been shown to exert an anti-inflammatory activity. Apolipoprotein-E (ApoE) is strongly associated with atherosclerosis and Alzheimer’s disease (AD). This study aimed to explore the therapeutic effect of β-OHB in the brain and the aorta of high-fat diet (HFD)-fed ApoE-deficient mice. We found in Apo-E deficient mice that β-OHB attenuated lipid deposition in the choroid plexus (ChP) and decreased amyloid plaque in the substantia nigra pars compacta. We also found decreased CD68-positive macroglia infiltration of the ChP in β-OHB-treated ApoE-deficient mice. β-OHB treatment ameliorated IgG extravasation into the hippocampal region of the brain. In vitro study using ChP mice cell line revealed that β-OHB attenuated oxidized low-density lipoprotein-induced ApoE-specific differentially expressed inflammatory ChP genes. Treatment with β-OHB reduced aortic plaque formation without affecting blood lipid profiles and decreased serum production of resistin, a well-established risk factor for both AD and atherosclerosis. Thus, the current study suggests and describes the therapeutic potential of β-OHB for the treatment of AD and atherosclerosis.

Bioavailability and Pharmaco-therapeutic Potential of Luteolin in Overcoming Alzheimer’s Disease

2019 ◽  
Vol 18 (5) ◽  
pp. 352-365 ◽  
Author(s):  
Fahad Ali ◽  
Yasir Hasan Siddique
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
In Vivo Models ◽  
Naturally Occurring ◽  
Current Review ◽  
Tau Aggregation ◽  
Dose Limiting Toxicity

Luteolin is a naturally occurring, yellow crystalline flavonoid found in numerous dietary supplements we frequently have in our meals. Studies in the last 2 decades have revealed its therapeutic potential to reduce the Alzheimer’s disease (AD) symptoms in various in vitro and in vivo models. The anti-Alzheimer’s potential of luteolin is attributed to its ability to suppress Aβ as well as tau aggregation or promote their disaggregation, down-regulate the expression of COX-2, NOS, MMP-9, TNF-α, interleukins and chemokines, reduce oxidative stress by scavenging ROS, modulate the activities of transcription factors CREB, cJun, Nrf-1, NF-κB, p38, p53, AP-1 and β-catenine and inhibiting the activities of various protein kinases. In several systems, luteolin has been described as a potent antioxidant and anti-inflammatory agent. In addition, we have also discussed about the bio-availability of the luteolin in the plasma. After being metabolized luteolin persists in plasma as glucuronides and sulphate-conjugates. Human clinical trials indicated no dose limiting toxicity when administered at a dose of 100 mg/day. Improvements in the formulations and drug delivery systems may further enhance the bioavailability and potency of luteolin. The current review describes in detail the data supporting these studies.

scholarly journals Therapeutic Potential of Dental Pulp Stem Cell Secretome for Alzheimer’s Disease Treatment: An In Vitro Study

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Nermeen El-Moataz Bellah Ahmed ◽  
Masashi Murakami ◽  
Yujiro Hirose ◽  
Misako Nakashima
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Dental Pulp ◽  
Therapeutic Potential ◽  
Late Onset ◽  
In Vitro Study ◽  
Promising Source

The secretome obtained from stem cell cultures contains an array of neurotrophic factors and cytokines that might have the potential to treat neurodegenerative conditions. Alzheimer’s disease (AD) is one of the most common human late onset and sporadic neurodegenerative disorders. Here, we investigated the therapeutic potential of secretome derived from dental pulp stem cells (DPSCs) to reduce cytotoxicity and apoptosis caused by amyloid beta (Aβ) peptide. We determined whether DPSCs can secrete the Aβ-degrading enzyme, neprilysin (NEP), and evaluated the effects of NEP expression in vitro by quantitating Aβ-degrading activity. The results showed that DPSC secretome contains higher concentrations of VEGF, Fractalkine, RANTES, MCP-1, and GM-CSF compared to those of bone marrow and adipose stem cells. Moreover, treatment with DPSC secretome significantly decreased the cytotoxicity of Aβpeptide by increasing cell viability compared to nontreated cells. In addition, DPSC secretome stimulated the endogenous survival factor Bcl-2 and decreased the apoptotic regulator Bax. Furthermore, neprilysin enzyme was detected in DPSC secretome and succeeded in degradingAβ1–42in vitro in 12 hours. In conclusion, our study demonstrates that DPSCs may serve as a promising source for secretome-based treatment of Alzheimer’s disease.

Development of a Nasal Donepezil-loaded Microemulsion for the Treatment of Alzheimer’s Disease: in vitro and ex vivo Characterization

2018 ◽  
Vol 17 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Lupe C. Espinoza ◽  
Marisol Vacacela ◽  
Beatriz Clares ◽  
Maria Luisa Garcia ◽  
Maria-Jose Fabrega ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Acetylcholinesterase Inhibitor ◽  
In Vitro Release ◽  
Nasal Irritation ◽  
Ex Vivo Permeation ◽  
Optical Stability

Background: Donepezil (DPZ) is widely prescribed as a specific and reversible acetylcholinesterase inhibitor for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). Objective: Considering the therapeutic potential of DPZ and the advantages offered by the intranasal route as an alternative for drug administration, the aim of this study was the development and characterization of a DPZ microemulsion (ME) for nose-to-brain delivery. Method: The ME was developed by construction of pseudoternary phase diagrams and characterized by dynamic light scattering and transmission electron microscopy. Flow properties and viscosity, as well as optical stability and stability under storage at different temperatures were evaluated. Finally, in vitro release and ex vivo permeation studies through porcine nasal mucosa were accomplished. Results: A transparent and homogeneous DPZ-ME (12.5 mg/ml) was obtained. The pH and viscosity were 6.38 and 44.69 mPa·s, respectively, indicating nasal irritation prevention and low viscosity. The mean droplet size was 58.9±3.2 nm with a polydispersity index of 0.19±0.04. The morphological analysis revealed the spherical shape of droplets, as well as their smooth and regular surface. Optical stability evidenced no destabilization processes. DPZ release profile indicated that the ME followed a hyperbolic kinetic model while the ex vivo permeation profile showed that the highest permeation occurred during initial 4 h and the maximum permeated amount was approximately 2000 µg, which corresponds to 80% of the starting amount of drug. Conclusion: We conclude that our nasal ME could be considered as a new potential tool for further investigation in the AD.

scholarly journals Astrocytic expression of the Alzheimer’s disease risk allele, ApoEε4, potentiates neuronal tau pathology in multiple preclinical models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Angela Marie Jablonski ◽  
Lee Warren ◽  
Marija Usenovic ◽  
Heather Zhou ◽  
Jonathan Sugam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Risk ◽  
In Vitro Models ◽  
Tau Pathology ◽  
Adeno Associated Virus ◽  
Human Apoe ◽  
Specific Effects ◽  
Tau Aggregation

AbstractApoEε4 is a major genetic risk factor for Alzheimer’s disease (AD), a disease hallmarked by extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). The presence of the ApoEε4 allele is associated with increased Aβ deposition and a role for ApoEε4 in the potentiation of tau pathology has recently emerged. This study focused on comparing the effects of adeno-associated virus (AAV)-mediated overexpression of the three predominant human ApoE isoforms within astrocytes. The isoform-specific effects of human ApoE were evaluated within in vitro models of tau pathology within neuron/astrocyte co-cultures, as well as in a transgenic tau mouse model. Tau aggregation, accumulation, and phosphorylation were measured to determine if the three isoforms of human ApoE had differential effects on tau. Astrocytic overexpression of the human ApoEε4 allele increased phosphorylation and misfolding of overexpressed neuronal tau in multiple models, including the aggregation and accumulation of added tau oligomers, in an isoform-specific manner. The ability of ApoEε4 to increase tau aggregation could be inhibited by an ApoEε4-specific antibody. This study indicates that astrocytic expression of ApoEε4 can potentiate tau aggregation and phosphorylation within neurons and supports a gain of toxic function hypothesis for the effect of hApoEε4 on tau.

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