Low molecular weight gut polyphenols metabolites and its nutritional relevance as effectors for attenuating neuroinflammation

AbstractThe burden of neurodegenerative disorders has been increasing as a consequence of a growing elderly population. These multifactorial diseases do not have a cure or efficient treatments. Due to its mechanistic complexity, prevention and treatment will require novel multi-targeted therapeutic strategies, targeting different disease hallmarks. The possibility of altering the progression and development of diseases through diet is an emerging as attractive approach with increasing supporting data. Epidemiological and clinical studies have highlighted the health potential of diets rich in fruits and vegetables. Studies with dietary (poly)phenols have been showing their multipotent and pleiotropic ability to modulate several cellular and molecular pathways and in that sense, dietary (poly)phenols can emerge as an alternative, with potential to be further explored. However, the precise contribution of dietary (poly)phenols and circulating (poly)phenol metabolites to human health is still in the beginning of being elucidated. Absorption and blood concentrations of some (poly)phenols is quite low, which can hamper the research in terms of understanding their effects in specific biomarkers of disease.The difficulty in demonstrating (poly)phenols true effects can also be justified by the uncertain metabolic fate that dietary (poly)phenols can have. In fact, it is necessary to identify the bioavailable metabolites resulting from (poly)phenol ingestion through the diet, as well as their ability to overcome and/or interact with cellular barriers and reach target tissues, in this case reach the brain. Having this in mind, it will be reviewed the current knowledge on the molecular mechanisms underlying (poly)phenol metabolites effects and their role on neuroinflammation one central hallmark, common in all neurodegenerative diseases.

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Bursting at the Seams: Molecular Mechanisms Mediating Astrocyte Swelling

International Journal of Molecular Sciences ◽

10.3390/ijms20020330 ◽

2019 ◽

Vol 20 (2) ◽

pp. 330 ◽

Cited By ~ 11

Author(s):

Audrey Lafrenaye ◽

J. Simard

Keyword(s):

Molecular Mechanisms ◽

Current Knowledge ◽

Predictors Of Outcome ◽

Cell Type ◽

Brain Swelling ◽

Astrocyte Swelling ◽

Health And Disease ◽

The One ◽

The Brain ◽

Cellular Swelling

Brain swelling is one of the most robust predictors of outcome following brain injury, including ischemic, traumatic, hemorrhagic, metabolic or other injury. Depending on the specific type of insult, brain swelling can arise from the combined space-occupying effects of extravasated blood, extracellular edema fluid, cellular swelling, vascular engorgement and hydrocephalus. Of these, arguably the least well appreciated is cellular swelling. Here, we explore current knowledge regarding swelling of astrocytes, the most abundant cell type in the brain, and the one most likely to contribute to pathological brain swelling. We review the major molecular mechanisms identified to date that contribute to or mitigate astrocyte swelling via ion transport, and we touch upon the implications of astrocyte swelling in health and disease.

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Rhombencephalitis Caused byListeria monocytogenesin Humans and Ruminants: A Zoonosis on the Rise?

Interdisciplinary Perspectives on Infectious Diseases ◽

10.1155/2010/632513 ◽

2010 ◽

Vol 2010 ◽

pp. 1-22 ◽

Cited By ~ 42

Author(s):

Anna Oevermann ◽

Andreas Zurbriggen ◽

Marc Vandevelde

Keyword(s):

Listeria Monocytogenes ◽

High Mortality ◽

Host Species ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Therapeutic Strategies ◽

Zoonotic Infection ◽

Cns Disease ◽

The Brain

Listeriosis is an emerging zoonotic infection of humans and ruminants worldwide caused byListeria monocytogenes(LM). In both host species, CNS disease accounts for the high mortality associated with listeriosis and includes rhombencephalitis, whose neuropathology is strikingly similar in humans and ruminants. This review discusses the current knowledge about listeric encephalitis, and involved host and bacterial factors. There is an urgent need to study the molecular mechanisms of neuropathogenesis, which are poorly understood. Such studies will provide a basis for the development of new therapeutic strategies that aim to prevent LM from invading the brain and spread within the CNS.

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Elucidating the Multi-Targeted Role of Nutraceuticals: A Complementary Therapy to Starve Neurodegenerative Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22084045 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4045

Author(s):

Tapan Behl ◽

Gagandeep Kaur ◽

Aayush Sehgal ◽

Sukhbir Singh ◽

Saurabh Bhatia ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Mechanisms ◽

Financial Burden ◽

Complementary Therapy ◽

Therapeutic Interventions ◽

Multifactorial Diseases ◽

Mitochondrial Homeostasis ◽

Attractive Option ◽

The Brain

The mechanisms underlying multifactorial diseases are always complex and challenging. Neurodegenerative disorders (NDs) are common around the globe, posing a critical healthcare issue and financial burden to the country. However, integrative evidence implies some common shared mechanisms and pathways in NDs, which include mitochondrial dysfunction, neuroinflammation, oxidative stress, intracellular calcium overload, protein aggregates, oxidative stress (OS), and neuronal destruction in specific regions of the brain, owing to multifaceted pathologies. The co-existence of these multiple pathways often limits the advantages of available therapies. The nutraceutical-based approach has opened the doors to target these common multifaceted pathways in a slow and more physiological manner to starve the NDs. Peer-reviewed articles were searched via MEDLINE and PubMed published to date for in-depth research and database collection. Considered to be complementary therapy with current clinical management and common drug therapy, the intake of nutraceuticals is considered safe to target multiple mechanisms of action in NDs. The current review summarizes the popular nutraceuticals showing different effects (anti-inflammatory, antioxidant, neuro-protectant, mitochondrial homeostasis, neurogenesis promotion, and autophagy regulation) on vital molecular mechanisms involved in NDs, which can be considered as complementary therapy to first-line treatment. Moreover, owing to its natural source, lower toxicity, therapeutic interventions, biocompatibility, potential nutritional effects, and presence of various anti-oxidative and neuroprotective constituents, the nutraceuticals serve as an attractive option to tackle NDs.

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The physiology of regulated BDNF release

Cell and Tissue Research ◽

10.1007/s00441-020-03253-2 ◽

2020 ◽

Vol 382 (1) ◽

pp. 15-45 ◽

Cited By ~ 5

Author(s):

Tanja Brigadski ◽

Volkmar Leßmann

Keyword(s):

Molecular Mechanisms ◽

Current Knowledge ◽

Detailed Knowledge ◽

Cellular Regulation ◽

Bdnf Expression ◽

Physiological Conditions ◽

Brain Circuits ◽

Important Regulator ◽

Network Plasticity ◽

The Brain

Abstract The neurotrophic factor BDNF is an important regulator for the development of brain circuits, for synaptic and neuronal network plasticity, as well as for neuroregeneration and neuroprotection. Up- and downregulations of BDNF levels in human blood and tissue are associated with, e.g., neurodegenerative, neurological, or even cardiovascular diseases. The changes in BDNF concentration are caused by altered dynamics in BDNF expression and release. To understand the relevance of major variations of BDNF levels, detailed knowledge regarding physiological and pathophysiological stimuli affecting intra- and extracellular BDNF concentration is important. Most work addressing the molecular and cellular regulation of BDNF expression and release have been performed in neuronal preparations. Therefore, this review will summarize the stimuli inducing release of BDNF, as well as molecular mechanisms regulating the efficacy of BDNF release, with a focus on cells originating from the brain. Further, we will discuss the current knowledge about the distinct stimuli eliciting regulated release of BDNF under physiological conditions.

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Spirulina Microalgae and Brain Health: A Scoping Review of Experimental and Clinical Evidence

Marine Drugs ◽

10.3390/md19060293 ◽

2021 ◽

Vol 19 (6) ◽

pp. 293

Author(s):

Vincenzo Sorrenti ◽

Davide Augusto Castagna ◽

Stefano Fortinguerra ◽

Alessandro Buriani ◽

Giovanni Scapagnini ◽

...

Keyword(s):

Cognitive Skills ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Vascular Wall ◽

Endothelial Damage ◽

Brain Health ◽

Brain Vessels ◽

Malnourished Children ◽

The Brain

Spirulina microalgae contain a plethora of nutrient and non-nutrient molecules providing brain health benefits. Numerous in vivo evidence has provided support for the brain health potential of spirulina, highlighting antioxidant, anti-inflammatory, and neuroprotective mechanisms. Preliminary clinical studies have also suggested that spirulina can help to reduce mental fatigue, protect the vascular wall of brain vessels from endothelial damage and regulate internal pressure, thus contributing to the prevention and/or mitigating of cerebrovascular conditions. Furthermore, the use of spirulina in malnourished children appears to ameliorate motor, language, and cognitive skills, suggesting a reinforcing role in developmental mechanisms. Evidence of the central effect of spirulina on appetite regulation has also been shown. This review aims to understand the applicative potential of spirulina microalgae in the prevention and mitigation of brain disorders, highlighting the nutritional value of this “superfood”, and providing the current knowledge on relevant molecular mechanisms in the brain associated with its dietary introduction.

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Effects of Radiation Therapy on Neural Stem Cells

Genes ◽

10.3390/genes10090640 ◽

2019 ◽

Vol 10 (9) ◽

pp. 640 ◽

Cited By ~ 6

Author(s):

Anna Michaelidesová ◽

Jana Konířová ◽

Petr Bartůněk ◽

Martina Zíková

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Side Effects ◽

Neural Stem Cells ◽

Neural Stem Cell ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Brain Radiotherapy ◽

The Impact ◽

The Brain

Brain and nervous system cancers in children represent the second most common neoplasia after leukemia. Radiotherapy plays a significant role in cancer treatment; however, the use of such therapy is not without devastating side effects. The impact of radiation-induced damage to the brain is multifactorial, but the damage to neural stem cell populations seems to play a key role. The brain contains pools of regenerative neural stem cells that reside in specialized neurogenic niches and can generate new neurons. In this review, we describe the advances in radiotherapy techniques that protect neural stem cell compartments, and subsequently limit and prevent the occurrence and development of side effects. We also summarize the current knowledge about neural stem cells and the molecular mechanisms underlying changes in neural stem cell niches after brain radiotherapy. Strategies used to minimize radiation-related damages, as well as new challenges in the treatment of brain tumors are also discussed.

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Uptake and metabolism of iron and iron oxide nanoparticles in brain astrocytes

Biochemical Society Transactions ◽

10.1042/bst20130114 ◽

2013 ◽

Vol 41 (6) ◽

pp. 1588-1592 ◽

Cited By ~ 29

Author(s):

Michaela C. Hohnholt ◽

Ralf Dringen

Keyword(s):

Iron Oxide ◽

Iron Oxide Nanoparticles ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Short Review ◽

Oxide Nanoparticles ◽

Iron Ions ◽

Iron Storage ◽

Cultured Astrocytes ◽

The Brain

Astrocytes are considered key regulators of the iron metabolism of the brain. These cells are able to rapidly accumulate iron ions and various iron-containing compounds, store iron efficiently in ferritin and also export iron. The present short review summarizes our current knowledge of the molecular mechanisms involved in the handling of iron by astrocytes. Cultured astrocytes efficiently take up iron as ferrous or ferric iron ions or as haem by specific iron transport proteins in their cell membrane. In addition, astrocytes accumulate large amounts of iron oxide nanoparticles by endocytotic mechanisms. Despite the rapid accumulation of high amounts of iron from various iron-containing sources, the viability of astrocytes is hardly affected. A rather slow liberation of iron from accumulated haem or iron oxide nanoparticles as well as the strong up-regulation of the synthesis of the iron storage protein ferritin are likely to contribute to the high resistance of astrocytes to iron toxicity. The efficient uptake of extracellular iron by cultured astrocytes as well as their strong up-regulation of ferritin after iron exposure also suggests that brain astrocytes deal well with an excess of iron and protect the brain against iron-mediated toxicity.

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Cellular Mechanisms of Melatonin: Insight from Neurodegenerative Diseases

Biomolecules ◽

10.3390/biom10081158 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1158 ◽

Cited By ~ 4

Author(s):

Dongmei Chen ◽

Tao Zhang ◽

Tae Ho Lee

Keyword(s):

Neurodegenerative Diseases ◽

Neurodegenerative Disorders ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Cellular Mechanisms ◽

Wide Range ◽

Public Health Challenge ◽

Cumulative Evidence ◽

The Brain ◽

Lateral Sclerosis

Neurodegenerative diseases are the second most common cause of death and characterized by progressive impairments in movement or mental functioning in the central or peripheral nervous system. The prevention of neurodegenerative disorders has become an emerging public health challenge for our society. Melatonin, a pineal hormone, has various physiological functions in the brain, including regulating circadian rhythms, clearing free radicals, inhibiting biomolecular oxidation, and suppressing neuroinflammation. Cumulative evidence indicates that melatonin has a wide range of neuroprotective roles by regulating pathophysiological mechanisms and signaling pathways. Moreover, melatonin levels are decreased in patients with neurodegenerative diseases. In this review, we summarize current knowledge on the regulation, molecular mechanisms and biological functions of melatonin in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, vascular dementia and multiple sclerosis. We also discuss the clinical application of melatonin in neurodegenerative disorders. This information will lead to a better understanding of the regulation of melatonin in the brain and provide therapeutic options for the treatment of various neurodegenerative diseases.

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Mesophyll conductance: the leaf corridors for photosynthesis

Biochemical Society Transactions ◽

10.1042/bst20190312 ◽

2020 ◽

Vol 48 (2) ◽

pp. 429-439 ◽

Cited By ~ 3

Author(s):

Jorge Gago ◽

Danilo M. Daloso ◽

Marc Carriquí ◽

Miquel Nadal ◽

Melanie Morales ◽

...

Keyword(s):

Molecular Mechanisms ◽

Current Knowledge ◽

Main Role ◽

Mesophyll Conductance ◽

Future Studies ◽

Cell Structures ◽

Leaf Tissues ◽

Change Framework ◽

Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

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Molecular Docking, Synthesis and anti-HIV-1 Protease Activity of Novel Chalcones

Current Pharmaceutical Design ◽

10.2174/1381612826666200203125557 ◽

2020 ◽

Vol 26 (8) ◽

pp. 802-814 ◽

Cited By ~ 3

Author(s):

Nemanja Turkovic ◽

Branka Ivkovic ◽

Jelena Kotur-Stevuljevic ◽

Milica Tasic ◽

Bojan Marković ◽

...

Keyword(s):

Molecular Weight ◽

Molecular Docking ◽

Chemical Synthesis ◽

Protease Activity ◽

Molecular Mechanisms ◽

Replication Cycle ◽

Low Molecular Weight ◽

Chalcone Derivatives ◽

Anti Hiv ◽

Hiv 1

Background: Since the beginning of the HIV/AIDS epidemic, 75 million people have been infected with the HIV and about 32 million people have died of AIDS. Investigation of the molecular mechanisms critical to the HIV replication cycle led to the identification of potential drug targets for AIDS therapy. One of the most important discoveries is HIV-1 protease, an enzyme that plays an essential role in the replication cycle of HIV. Objective: The aim of the present study is to synthesize and investigate anti-HIV-1 protease activity of some chalcone derivatives with the hope of discovering new lead structure devoid drug resistance. Methods: 20 structurally similar chalcone derivatives were synthesized and their physico-chemical characterization was performed. Binding of chalcones to HIV-1 protease was investigated by fluorimetric assay. Molecular docking studies were conducted to understand the interactions. Results: The obtained results revealed that all compounds showed anti-HIV-1 protease activity. Compound C1 showed the highest inhibitory activity with an IC50 value of 0.001 μM, which is comparable with commercial product Darunavir. Conclusion: It is difficult to provide general principles of inhibitor design. Structural properties of the compounds are not the only consideration; ease of chemical synthesis, low molecular weight, bioavailability, and stability are also of crucial importance. Compared to commercial products the main advantage of compound C1 is the ease of chemical synthesis and low molecular weight. Furthermore, compound C1 has a structure that is different to peptidomimetics, which could contribute to its stability and bioavailability.

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