scholarly journals Proteomic changes induced by harmine in human brain organoids reveal signaling pathways related to neuroprotection

2021 ◽  
Author(s):  
Karina Karmirian ◽  
Lívia Goto-Silva ◽  
Juliana Minardi Nascimento ◽  
Marcelo N Costa ◽  
José Alexandre Salerno ◽  
...  
Keyword(s):  
Human Brain ◽  
Intracellular Transport ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Therapeutic Potential ◽  
Antioxidant Activities ◽  
Cellular Mechanisms ◽  
Neuroprotective Effects ◽  
Vesicle Cycle ◽  
Neurotrophin Signaling

Harmine is a β-carboline found in Banisteriopsis caapi, a constituent of ayahuasca brew. Ayahuasca is consumed as a beverage in native Americans' sacred rituals and in religious ceremonies in Brazil. Throughout the years, the beneficial effects of ayahuasca to improve mental health and life quality have been reported, which propelled the investigation of its therapeutic potential to target neurological disorders such as depression and anxiety. Indeed, antidepressant effects of ayahuasca have been described, raising the question of which cellular mechanisms might underlie those effects. Previous animal studies describe potential neuroprotective mechanisms of harmine, including anti-inflammatory and antioxidant activities, and neurotrophin signaling activation. However, the cellular and molecular mechanisms modulated by harmine in human models remain less investigated. Here we analyzed the short-term changes in the proteome of human brain organoids treated with harmine using shotgun mass spectrometry. Harmine upregulates proteins related to synaptic vesicle cycle, cytoskeleton-dependent intracellular transport, cell cycle, glucose transporter-4 translocation, and neurotrophin signaling pathway. In addition, protein expression levels of Akt and phosphorylated CREB were increased after 24 hour-treatment. Our results shed light on the potential mechanisms that may underlie harmine-induced neuroprotective effects.

Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential

2020 ◽  
Vol 26 ◽  
Author(s):  
Nimra Javaid ◽  
Muhammad Ajmal Shah ◽  
Azhar Rasul ◽  
Zunera Chauhdary ◽  
Uzma Saleem ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ellagic Acid ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Acetylcholinesterase Activity ◽  
Neuroprotective Effects

: Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead towards neuronal cell death. Alzheimer’s disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset yet later on it worsens. The documented evidence of AD neuropathology manifested the neuro-inflammation, increased reactive oxygen, nitrogen species and decreased antioxidant protective process; mitochondrial dysfunction as well as increased level of acetylcholinesterase activity. Moreover, enhanced action of proteins leads towards neural apoptosis which have a vital role in the degeneration of neurons. The inability of commercial therapeutic options to treat AD with targeting single mechanism leads the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid, latest studies expressed that ellagic acid can initiate the numerous cell signaling transmission and decrease the progression of disorders, involved in the degeneration of neurons. The influential property of ellagic acid to protect the neurons in neurodegenerative disorders is due to its antioxidant effect, iron chelating and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mode of action of ellagic acid against neurodegeneration.

Cordycepin Exerts Neuroprotective Effects via an Anti-Apoptotic Mechanism based on the Mitochondrial Pathway in a Rotenone-Induced Parkinsonism Rat Model

2019 ◽  
Vol 18 (8) ◽  
pp. 609-620 ◽  
Author(s):  
Xin Jiang ◽  
Pei-Chen Tang ◽  
Qin Chen ◽  
Xin Zhang ◽  
Yi-Yun Fan ◽  
...  
Keyword(s):  
Rat Model ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Neuroprotective Effects ◽  
Cyt C

Background: Cordycepin (Cor), one of the major bioactive components of the traditional Chinese medicine Cordyceps militaris, has been used in clinical practice for several years. However, its neuroprotective effect remains unknown. Aim: The purpose of the study was to evaluate the neuroprotective effects of Cor using a rotenoneinduced Parkinson’s Disease (PD) rat model and to delineate the possible associated molecular mechanisms. Methods: In vivo, behavioural tests were performed based on the 10-point scale and grid tests. Levels of dopamine and its metabolites in the striatum and the numbers of TH-positive neurons in the Substantia Nigra pars compacta (SNpc) were investigated by high-performance liquid chromatography with electrochemical detection and immunohistochemical staining, respectively. In vitro, cell apoptosis rates and Mitochondrial Membrane Potential (MMP) were analysed by flow cytometry and the mRNA and protein levels of Bax, Bcl-2, Bcl-xL, Cytochrome c (Cyt-c), and caspase-3 were determined by quantitative real-time PCR and western blotting. Results: Showed that Cor significantly improved dyskinesia, increased the numbers of TH-positive neurons in the SNpc, and maintained levels of dopamine and its metabolites in the striatum in rotenone- induced PD rats. We also found that apoptosis was suppressed and the loss of MMP was reversed with Cor treatment. Furthermore, Cor markedly down-regulated the expression of Bax, upregulated Bcl-2 and Bcl-xL, inhibited the activation of caspase-3, and decreased the release of Cyt-c from the mitochondria to the cytoplasm, as compared to those in the rotenone-treated group. Conclusion: Therefore, Cor protected dopamine neurons against rotenone-induced apoptosis by improving mitochondrial dysfunction in a PD model, demonstrating its therapeutic potential for this disease.

A review on chemistry, source and therapeutic potential of lambertianic acid

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Md Shahinozzaman ◽  
Moutushi Islam ◽  
Bristy Basak ◽  
Arifa Sultana ◽  
Rashiduzzaman Emran ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Bioactive Compound ◽  
Cancer Cell Proliferation ◽  
Neuroprotective Effects ◽  
Potential Health ◽  
Anticancer Properties ◽  
Toxicological Profile ◽  
Lambertianic Acid

Abstract Lambertianic acid (LA) is a diterpene bioactive compound mainly purified from different species of Pinus. It is an optical isomer of another natural compound daniellic acid and was firstly purified from Pinus lambertiana. LA can be synthesized in laboratory from podocarpic acid. It has been reported to have potential health benefits in attenuating obesity, allergies and different cancers including breast, liver, lung and prostate cancer. It exhibits anticancer properties through inhibiting cancer cell proliferation and survival, and inducing apoptosis, targeting major signalling components including AKT, AMPK, NFkB, COX-2, STAT3, etc. Most of the studies with LA were done using in vitro models, thus warranting future investigations with animal models to evaluate its pharmacological effects such as antidiabetic, anti-inflammatory and neuroprotective effects as well as to explore the underlying molecular mechanisms and toxicological profile. This review describes the chemistry, source, purification and therapeutic potentials of LA and it can therefore be a suitable guideline for any future study with LA.

Extracts from Dendropanax morbifera Leaves Have Modulatory Effects on Neuroinflammation in Microglia

2016 ◽  
Vol 44 (01) ◽  
pp. 119-132 ◽  
Author(s):  
Hyun-Jung Shim ◽  
Sinwoo Park ◽  
Ji-Won Lee ◽  
Hye-Jin Park ◽  
Seung-Hoon Baek ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Marker Genes ◽  
Cellular Mechanisms ◽  
Line Production ◽  
Bv2 Cells ◽  
Study Results ◽  
Dendropanax Morbifera ◽  
Pro Inflammatory Cytokines

Dendropanax morbifera (D. morbifera), a species endemic to Korea, is largely distributed throughout the southern part of the country. Its leaves, stems, roots, and seeds have been used as a form of alternative medicine for various diseases and neurological disorders including paralysis, stroke, and migraine. However, the molecular mechanisms that underlie the remedial effects of D. morbifera remain largely unknown. In this paper, extracts from D. morbifera leaves were prepared using ethyl acetate as a solvent (abbreviated as DMLE). The modulatory effects of DMLE on neuroinflammation were studied in a lipopolysaccharide (LPS)-stimulated BV2 murine microglial cell line. Production of pro-inflammatory cytokines, activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-[Formula: see text]B), and different M1/M2 activation states of microglia were examined. DMLE treatment suppressed the production of pro-inflammatory cytokines including tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-6 (IL-6), and nitric oxide (NO) in LPS-stimulated BV2 cells. DMLE treatment also attenuated the activation of MAPKs and NF-[Formula: see text]B. In a novel discovery, we found that DMLE up-regulated the marker genes representing an alternative, anti-inflammatory M2 polarization, while suppressing the expression of the classical, pro-inflammatory M1 activation state genes. Here, we uncovered the cellular mechanisms underlying the beneficial effects of D. morbifera against neuroinflammation using BV2 microglia cells. These results strongly suggest that DMLE was able to counter the effects of LPS on BV2 cells via control of microglia polarization states. Additionally, study results indicated that DMLE may have therapeutic potential as a neuroinflammation-suppressing treatment for neurodegenerative diseases.

scholarly journals Resveratrol as a Therapeutic Agent for Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Teng Ma ◽  
Meng-Shan Tan ◽  
Jin-Tai Yu ◽  
Lan Tan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Agent ◽  
Red Wine ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Neuroprotective Effects

Alzheimer’s disease (AD) is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβaccumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD.

scholarly journals Molecular Mechanisms Responsible for Therapeutic Potential of Mesenchymal Stem Cell-Derived Secretome

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 467 ◽  
Author(s):  
Carl Harrell ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
Nebojsa Arsenijevic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Genetic Material ◽  
Cell Number ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Cellular Mechanisms ◽  
Tissue Repair And Regeneration

Mesenchymal stem cell (MSC)-sourced secretome, defined as the set of MSC-derived bioactive factors (soluble proteins, nucleic acids, lipids and extracellular vesicles), showed therapeutic effects similar to those observed after transplantation of MSCs. MSC-derived secretome may bypass many side effects of MSC-based therapy, including unwanted differentiation of engrafted MSCs. In contrast to MSCs which had to be expanded in culture to reach optimal cell number for transplantation, MSC-sourced secretome is immediately available for treatment of acute conditions, including fulminant hepatitis, cerebral ischemia and myocardial infarction. Additionally, MSC-derived secretome could be massively produced from commercially available cell lines avoiding invasive cell collection procedure. In this review article we emphasized molecular and cellular mechanisms that were responsible for beneficial effects of MSC-derived secretomes in the treatment of degenerative and inflammatory diseases of hepatobiliary, respiratory, musculoskeletal, gastrointestinal, cardiovascular and nervous system. Results obtained in a large number of studies suggested that administration of MSC-derived secretomes represents a new, cell-free therapeutic approach for attenuation of inflammatory and degenerative diseases. Therapeutic effects of MSC-sourced secretomes relied on their capacity to deliver genetic material, growth and immunomodulatory factors to the target cells enabling activation of anti-apoptotic and pro-survival pathways that resulted in tissue repair and regeneration.

The Genetics of Primary Microcephaly

2018 ◽  
Vol 19 (1) ◽  
pp. 177-200 ◽  
Author(s):  
Divya Jayaraman ◽  
Byoung-Il Bae ◽  
Christopher A. Walsh
Keyword(s):  
Intracellular Transport ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Brain Size ◽  
Brain Evolution ◽  
Primary Microcephaly ◽  
Cellular Mechanisms ◽  
Functional Studies ◽  
Metabolic Conditions ◽  
And Gender

Primary microcephaly (MCPH, for “microcephaly primary hereditary”) is a disorder of brain development that results in a head circumference more than 3 standard deviations below the mean for age and gender. It has a wide variety of causes, including toxic exposures, in utero infections, and metabolic conditions. While the genetic microcephaly syndromes are relatively rare, studying these syndromes can reveal molecular mechanisms that are critical in the regulation of neural progenitor cells, brain size, and human brain evolution. Many of the causative genes for MCPH encode centrosomal proteins involved in centriole biogenesis. However, other MCPH genes fall under different mechanistic categories, notably DNA replication and repair. Recent gene discoveries and functional studies have implicated novel cellular processes, such as cytokinesis, centromere and kinetochore function, transmembrane or intracellular transport, Wnt signaling, and autophagy, as well as the apical polarity complex. Thus, MCPH genes implicate a wide variety of molecular and cellular mechanisms in the regulation of cerebral cortical size during development.

scholarly journals Bipolar disorder: leads from the molecular and cellular mechanisms of action of mood stabilisers

2001 ◽  
Vol 178 (S41) ◽  
pp. s107-s119 ◽  
Author(s):  
Husseini K. Manji ◽  
Gregory J. Moore ◽  
Guang Chen
Keyword(s):  
Molecular Mechanisms ◽  
Chronic Administration ◽  
Binding Activity ◽  
Therapeutic Effects ◽  
Activator Protein 1 ◽  
Cellular Mechanisms ◽  
Neuroprotective Effects ◽  
Neuronal Communication ◽  
Dna Binding Activity ◽  
New Research

BackgroundNew research is dramatically altering our understanding of the molecular mechanisms underlying neuronal communication.AimTo elucidate the molecular mechanisms underlying the therapeutic effects of mood stabilisers.MethodResults from integrated clinical and laboratory studies are reviewed.ResultsChronic administration of lithium and valproate produced a striking reduction in protein kinase C (PKC) isozymes in rat frontal cortex and hippocampus. In a small study, tamoxifen (also a PKC inhibitor) had marked antimanic efficacy. Both lithium and valproate regulate the DNA binding activity of the activator protein 1 family of transcription factors. Using mRNA differential display, it was also shown that chronic administration of lithium and valproate modulates expression of several genes. An exciting finding is that of a robust elevation in the levels of the cytoprotective protein, bcl-2.ConclusionsThe results suggest that regulation of signalling pathways may play a major part in the long-term actions of mood stabilisers. Additionally, mood stabilisers may exert underappreciated neuroprotective effects.

Mesenchymal Stem Cell Therapy in Intracerebral Haemorrhagic Stroke

2018 ◽  
Vol 25 (19) ◽  
pp. 2176-2197 ◽  
Author(s):  
Gloria Bedini ◽  
Anna Bersano ◽  
Elisa R. Zanier ◽  
Francesca Pischiutta ◽  
Eugenio A. Parati
Keyword(s):  
Stem Cell ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Haemorrhagic Stroke ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Cell Therapies ◽  
Mesenchymal Stem Cell Therapy ◽  
High Degree

Background: Spontaneous intracerebral haemorrhage (ICH) is a relatively common fatal disease, with an overall global incidence estimated at 24.6 per 100,000 person- years. Given the high degree of morbidity and mortality associated with ICH, therapies that may have neuroprotective effects are of increasing interest to clinicians. In this last context, cell therapies offer the promise of improving the disease course which cannot be addressed adequately by existing treatments. Objective: The aim of this review is to evaluate the protective effects and molecular mechanisms of mesenchymal stem cells (MSCs) on haemorrhagic brain following ICH. We also discuss possible emerging therapeutic approaches worth of further research. Methods and Results: The available literature on the therapeutic potential of MSCs in ICH animal models clearly demonstrated that MSCs enhance the functional recovery and reduce the volume of the infarct size exerting anti-inflammatory and angiogenic properties. However, the quality of the original articles investigating the efficacy of stem cell therapies in ICH animal models is still poor and the lack of ICH clinical trial does not permit to reach any relevant conclusions. Conclusion: Further studies have to be implemented in order to achieve standardized methods of MSCs isolation, characterization and administration to improve ICH treatments with MSCs or MSC-derived products.

Dietary and developmental regulation of intestinal sugar transport

2001 ◽  
Vol 360 (2) ◽  
pp. 265-276 ◽  
Author(s):  
Ronaldo P. FERRARIS
Keyword(s):  
Small Intestine ◽  
Glucose Transport ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
De Novo ◽  
Sugar Transport ◽  
Transport Systems ◽  
Intestinal Lumen ◽  
Transport Activity ◽  
Cellular Mechanisms

The Na+-dependent glucose transporter SGLT1 and the facilitated fructose transporter GLUT5 absorb sugars from the intestinal lumen across the brush-border membrane into the cells. The activity of these transport systems is known to be regulated primarily by diet and development. The cloning of these transporters has led to a surge of studies on cellular mechanisms regulating intestinal sugar transport. However, the small intestine can be a difficult organ to study, because its cells are continuously differentiating along the villus, and because the function of absorptive cells depends on both their state of maturity and their location along the villus axis. In this review, I describe the typical patterns of regulation of transport activity by dietary carbohydrate, Na+ and fibre, how these patterns are influenced by circadian rhythms, and how they vary in different species and during development. I then describe the molecular mechanisms underlying these regulatory patterns. The expression of these transporters is tightly linked to the villus architecture; hence, I also review the regulatory processes occurring along the crypt-villus axis. Regulation of glucose transport by diet may involve increased transcription of SGLT1 mainly in crypt cells. As cells migrate to the villus, the mRNA is degraded, and transporter proteins are then inserted into the membrane, leading to increases in glucose transport about a day after an increase in carbohydrate levels. In the SGLT1 model, transport activity in villus cells cannot be modulated by diet. In contrast, GLUT5 regulation by the diet seems to involve de novo synthesis of GLUT5 mRNA synthesis and protein in cells lining the villus, leading to increases in fructose transport a few hours after consumption of diets containing fructose. In the GLUT5 model, transport activity can be reprogrammed in mature enterocytes lining the villus column. Innovative experimental approaches are needed to increase our understanding of sugar transport regulation in the small intestine. I close by suggesting specific areas of research that may yield important information about this interesting, but difficult, topic.

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