scholarly journals Anti-aggregation Effects of Phenolic Compounds on α-synuclein

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2444
Author(s):  
Kenjiro Ono ◽  
Mayumi Tsuji ◽  
Tritia R. Yamasaki ◽  
Giulio M. Pasinetti
Keyword(s):  
Phenolic Compounds ◽  
Gut Microbiota ◽  
Lewy Bodies ◽  
Hydroxybenzoic Acid ◽  
Dietary Polyphenols ◽  
Pathologic Features ◽  
Hydroxyphenylacetic Acid ◽  
A Cell ◽  
The Brain

The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson’s disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that attenuate αS aggregation and propagation. Based on cumulative evidence that αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies, we and other groups reported that phenolic compounds inhibit αS aggregation including oligomerization, thereby ameliorating αS oligomer-induced cellular and synaptic toxicities. Heterogeneity in gut microbiota may influence the efficacy of dietary polyphenol metabolism. Our recent studies on the brain-penetrating polyphenolic acids 3-hydroxybenzoic acid (3-HBA), 3,4-dihydroxybenzoic acid (3,4-diHBA), and 3-hydroxyphenylacetic acid (3-HPPA), which are derived from gut microbiota-based metabolism of dietary polyphenols, demonstrated an in vitro ability to inhibit αS oligomerization and mediate aggregated αS-induced neurotoxicity. Additionally, 3-HPPA, 3,4-diHBA, 3-HBA, and 4-hydroxybenzoic acid significantly attenuated intracellular αS seeding aggregation in a cell-based system. This review focuses on recent research developments regarding neuroprotective properties, especially anti-αS aggregation effects, of phenolic compounds and their metabolites by the gut microbiome, including our findings in the pathogenesis of α-synucleinopathies.

Biodiversity as a source of new pharmacophores: A new theory of memory III

2005 ◽  
Vol 77 (1) ◽  
pp. 75-81 ◽  
Author(s):  
◽  
M. Iqbal Choudhary
Keyword(s):  
Natural Products ◽  
Anticancer Agents ◽  
Neurological Disorders ◽  
In Vitro Bioassay ◽  
Natural Sources ◽  
Chemical Basis ◽  
Antioxidant Agents ◽  
A Cell ◽  
The Brain

Several classes of natural products with significant inhibitory activity against target enzymes involved in several diseases have been identified. Spectrophotometer and high-throughput assays were used to assess the inhibition of prolyl endopeptidase (PEP), which led us to some novel inhibitors having potential as anticancer agents. Inhibition of cholinesterase enzymes has led to the discovery of new inhibitors with potential for use in Alzheimer’s disease and other neurological disorders. We have also discovered several potent antioxidant agents from natural sources by using a battery of antioxidant assays. Anti-inflammatory activity of a number of natural products was assayed through a cell-based in vitro bioassay. This article also contains a section on a slightly different topic of chemical basis of memory as presented during the lecture. The theory of the chemical basis of memory based on hydrogen bonding in the brain is further elaborated.

scholarly journals Parkinson’s disease is a type of amyloidosis featuring accumulation of amyloid fibrils of α-synuclein

2019 ◽  
Vol 116 (36) ◽  
pp. 17963-17969 ◽  
Author(s):  
Katsuya Araki ◽  
Naoto Yagi ◽  
Koki Aoyama ◽  
Chi-Jing Choong ◽  
Hideki Hayakawa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Amyloid Fibrils ◽  
Lewy Bodies ◽  
X Ray Diffraction ◽  
Thin Sections ◽  
X Ray ◽  
Β Sheet ◽  
The Brain

Many neurodegenerative diseases are characterized by the accumulation of abnormal protein aggregates in the brain. In Parkinson’s disease (PD), α-synuclein (α-syn) forms such aggregates called Lewy bodies (LBs). Recently, it has been reported that aggregates of α-syn with a cross-β structure are capable of propagating within the brain in a prionlike manner. However, the presence of cross-β sheet-rich aggregates in LBs has not been experimentally demonstrated so far. Here, we examined LBs in thin sections of autopsy brains of patients with PD using microbeam X-ray diffraction (XRD) and found that some of them gave a diffraction pattern typical of a cross-β structure. This result confirms that LBs in the brain of PD patients contain amyloid fibrils with a cross-β structure and supports the validity of in vitro propagation experiments using artificially formed amyloid fibrils of α-syn. Notably, our finding supports the concept that PD is a type of amyloidosis, a disease featuring the accumulation of amyloid fibrils of α-syn.

scholarly journals A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization

2011 ◽  
Vol 194 (2) ◽  
pp. 277-289 ◽  
Author(s):  
Zohreh Khavandgar ◽  
Christophe Poirier ◽  
Christopher J. Clarke ◽  
Jingjing Li ◽  
Nicholas Wang ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Skeletal Development ◽  
Specific Expression ◽  
Neutral Sphingomyelinase ◽  
Phosphodiesterase 3 ◽  
A Cell ◽  
Endocrine Factors ◽  
The Brain ◽  
Bone Abnormalities

A deletion mutation called fro (fragilitas ossium) in the murine Smpd3 (sphingomyelin phosphodiesterase 3) gene leads to a severe skeletal dysplasia. Smpd3 encodes a neutral sphingomyelinase (nSMase2), which cleaves sphingomyelin to generate bioactive lipid metabolites. We examined endochondral ossification in embryonic day 15.5 fro/fro mouse embryos and observed impaired apoptosis of hypertrophic chondrocytes and severely undermineralized cortical bones in the developing skeleton. In a recent study, it was suggested that nSMase2 activity in the brain regulates skeletal development through endocrine factors. However, we detected Smpd3 expression in both embryonic and postnatal skeletal tissues in wild-type mice. To investigate whether nSMase2 plays a cell-autonomous role in these tissues, we examined the in vitro mineralization properties of fro/fro osteoblast cultures. fro/fro cultures mineralized less than the control osteoblast cultures. We next generated fro/fro;Col1a1-Smpd3 mice, in which osteoblast-specific expression of Smpd3 corrected the bone abnormalities observed in fro/fro embryos without affecting the cartilage phenotype. Our data suggest tissue-specific roles for nSMase2 in skeletal tissues.

scholarly journals Adhesion, Invasion, and Translocation Characteristics of Listeria monocytogenes Serotypes in Caco-2 Cell and Mouse Models

2003 ◽  
Vol 69 (6) ◽  
pp. 3640-3645 ◽  
Author(s):  
Ziad W. Jaradat ◽  
Arun K. Bhunia
Keyword(s):  
Listeria Monocytogenes ◽  
Mouse Model ◽  
Cell Line ◽  
Mouse Bioassay ◽  
Adhesion Properties ◽  
Culture Model ◽  
A Cell ◽  
In Vitro Adhesion ◽  
The Brain

ABSTRACT Adhesion is a crucial first step in Listeria monocytogenes pathogenesis. In this study, we examined how the adhesion properties of serotypes correlate with their invasion efficiencies in a cell culture model (Caco-2) and in a mouse model. Adhesion characteristics of all 13 serotypes of L. monocytogenes (25 strains) were analyzed, which yielded three distinct groups (P < 0.05) with high-, medium-, and low-level-adhesion profiles. The efficiency of these strains in invading the Caco-2 cell line was analyzed, which produced two groups; however, the overall correlation (R 2) was only 0.1236. In the mouse bioassay, all selected strains, irrespective of their adhesion profiles, translocated to the liver and the spleen with almost equal frequencies that did not show any clear relationship with adhesion profiles. However, the serotypes with increased adhesion showed a slightly increased translocation to the brain (R 2 = 0.3371). Collectively, these results indicate that an in vitro adhesion profile might not be an accurate assessment of a strain's ability to invade a cultured cell line or organs or tissues in a mouse model.

scholarly journals Efficient Protection of Probiotics for Delivery to the Intestinal tract by Cellulose Sulphate Encapsulation

2020 ◽  
Author(s):  
Walter Henry Gunzburg ◽  
Myo Myint Aung ◽  
Pauline Toa ◽  
Shirelle Ng ◽  
Eliot Read ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Cell Encapsulation ◽  
Stomach Acid ◽  
Intestinal Delivery ◽  
Subsequent Exposure ◽  
Probiotic Strains ◽  
A Cell ◽  
Cellulose Sulphate ◽  
Micro Organisms

Abstract Background: Gut microbiota in humans and animals play an important role in health, aiding in digestion, regulation of the immune system and protection against pathogens. Changes or imbalances in the gut microbiota (dysbiosis) have been linked to a variety of local and systemic diseases, and there is growing evidence that restoring the balance of the microbiota by delivery of probiotic micro-organisms can improve health. However, orally delivered probiotic micro-organisms must survive transit through lethal highly acid conditions of the stomach and bile salts in the small intestine. Current methods to protect probiotic micro-organisms are still not effective enough.Results : We have developed a cell encapsulation technology based on the natural polymer, cellulose sulphate (CS) that protects members of the microbiota from stomach acid and bile. Here we show that six commonly used probiotic strains (5 bacteria and 1 yeast) can be encapsulated within CS microspheres. These encapsulated strains survive low pH in vitro for up to 4 hours without appreciable loss in viability as compared to their respective non-encapsulated counterparts. They also survive subsequent exposure to bile. The CS microspheres can be digested by levels of cellulase found in the human intestine, indicating one mechanism of release. Studies in mice that were fed CS encapsulated autofluorescing, commensal E. coli demonstrated release and colonization of the intestinal tract.Conclusion: Taken together, the data suggests that CS microencapsulation can protect bacteria and yeast from viability losses due to stomach acid, allowing the use of lower oral doses of probiotics and microbiota, whilst ensuring good intestinal delivery and release.

scholarly journals α-synuclein pathogenesis in hiPSC models of Parkinson’s Disease

2021 ◽  
Author(s):  
Leo R Quinlan ◽  
Jara Maria Baena-Montes ◽  
Sahar Avazzadeh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Modeling ◽  
Viral Vector ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Lewy Bodies ◽  
Model Systems ◽  
The Brain

α-synuclein is an increasingly prominent player in the pathology of a variety of neurodegenerative conditions. Parkinson’s disease (PD) is a neurodegenerative disorder that affects mainly the dopaminergic neurons in the substantia nigra of the brain. Typical of PD pathology is the finding of protein aggregations termed ‘Lewy bodies’ in the brain regions affected. α-synuclein is implicated in many disease states including dementia with Lewy bodies and Alzheimer’s disease. However, PD is the most common synucleinopathy and continues to be a significant focus of PD research in terms of the α-synuclein Lewy body pathology. Mutations in several genes are associated with PD development including SNCA, which encodes α-synuclein. A variety of model systems have been employed to study α-synuclein physiology and pathophysiology in an attempt to relate more closely to PD pathology. These models include cellular and animal system exploring transgenic technologies, viral vector expression and knockdown approaches, and models to study the potential prion protein-like effects of α-synuclein. The current review focuses on human induced pluripotent stem cell (iPSC) models with a specific focus on mutations or multiplications of the SNCA gene. iPSCs are a rapidly evolving technology with huge promise in the study of normal physiology and disease modeling in vitro. The ability to maintain a patient's genetic background and replicate similar cell phenotypes make iPSCs a powerful tool in the study of neurological diseases. This review focus on the current knowledge about α-synuclein physiological function as well as its role in PD pathogenesis based on human iPSC models.

scholarly journals Efficient protection of microorganisms for delivery to the intestinal tract by cellulose sulphate encapsulation

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Walter H. Gunzburg ◽  
Myo Myint Aung ◽  
Pauline Toa ◽  
Shirelle Ng ◽  
Eliot Read ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Tract ◽  
Cell Encapsulation ◽  
Stomach Acid ◽  
Intestinal Delivery ◽  
Subsequent Exposure ◽  
Probiotic Strains ◽  
A Cell ◽  
Cellulose Sulphate

Abstract Background Gut microbiota in humans and animals play an important role in health, aiding in digestion, regulation of the immune system and protection against pathogens. Changes or imbalances in the gut microbiota (dysbiosis) have been linked to a variety of local and systemic diseases, and there is growing evidence that restoring the balance of the microbiota by delivery of probiotic microorganisms can improve health. However, orally delivered probiotic microorganisms must survive transit through lethal highly acid conditions of the stomach and bile salts in the small intestine. Current methods to protect probiotic microorganisms are still not effective enough. Results We have developed a cell encapsulation technology based on the natural polymer, cellulose sulphate (CS), that protects members of the microbiota from stomach acid and bile. Here we show that six commonly used probiotic strains (5 bacteria and 1 yeast) can be encapsulated within CS microspheres. These encapsulated strains survive low pH in vitro for at least 4 h without appreciable loss in viability as compared to their respective non-encapsulated counterparts. They also survive subsequent exposure to bile. The CS microspheres can be digested by cellulase at concentrations found in the human intestine, indicating one mechanism of release. Studies in mice that were fed CS encapsulated autofluorescing, commensal E. coli demonstrated release and colonization of the intestinal tract. Conclusion Taken together, the data suggests that CS microencapsulation can protect bacteria and yeasts from viability losses due to stomach acid, allowing the use of lower oral doses of probiotics and microbiota, whilst ensuring good intestinal delivery and release.

scholarly journals Novel approaches for analysing gut microbes and dietary polyphenols: challenges and opportunities

Microbiology ◽  
2010 ◽  
Vol 156 (11) ◽  
pp. 3224-3231 ◽  
Author(s):  
R. A. Kemperman ◽  
S. Bolca ◽  
L. C. Roger ◽  
E. E. Vaughan
Keyword(s):  
Gut Microbiota ◽  
Health Effects ◽  
Fruit And Vegetables ◽  
Human Gut ◽  
Microbial Composition ◽  
Dietary Polyphenols ◽  
Host Health ◽  
The Impact

Polyphenols, ubiquitously present in the food we consume, may modify the gut microbial composition and/or activity, and moreover, may be converted by the colonic microbiota to bioactive compounds that influence host health. The polyphenol content of fruit and vegetables and derived products is implicated in some of the health benefits bestowed on eating fruit and vegetables. Elucidating the mechanisms behind polyphenol metabolism is an important step in understanding their health effects. Yet, this is no trivial assignment due to the diversity encountered in both polyphenols and the gut microbial composition, which is further confounded by the interactions with the host. Only a limited number of studies have investigated the impact of dietary polyphenols on the complex human gut microbiota and these were mainly focused on single polyphenol molecules and selected bacterial populations. Our knowledge of gut microbial genes and pathways for polyphenol bioconversion and interactions is poor. Application of specific in vitro or in vivo models mimicking the human gut environment is required to analyse these diverse interactions. A particular benefit can now be gained from next-generation analytical tools such as metagenomics and metatranscriptomics allowing a wider, more holistic approach to the analysis of polyphenol metabolism. Understanding the polyphenol–gut microbiota interactions and gut microbial bioconversion capacity will facilitate studies on bioavailability of polyphenols in the host, provide more insight into the health effects of polyphenols and potentially open avenues for modulation of polyphenol bioactivity for host health.

scholarly journals Efficient Protection of Microorganisms for Delivery to the Intestinal tract by Cellulose Sulphate Encapsulation

2020 ◽  
Author(s):  
Walter Henry Gunzburg ◽  
Myo Myint Aung ◽  
Pauline Toa ◽  
Shirelle Ng ◽  
Eliot Read ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Tract ◽  
Cell Encapsulation ◽  
Stomach Acid ◽  
Intestinal Delivery ◽  
Subsequent Exposure ◽  
Probiotic Strains ◽  
A Cell ◽  
Cellulose Sulphate

Abstract Background Gut microbiota in humans and animals play an important role in health, aiding in digestion, regulation of the immune system and protection against pathogens. Changes or imbalances in the gut microbiota (dysbiosis) have been linked to a variety of local and systemic diseases, and there is growing evidence that restoring the balance of the microbiota by delivery of probiotic microorganisms can improve health. However, orally delivered probiotic microorganisms must survive transit through lethal highly acid conditions of the stomach and bile salts in the small intestine. Current methods to protect probiotic microorganisms are still not effective enough.Results We have developed a cell encapsulation technology based on the natural polymer, cellulose sulphate (CS) that protects members of the microbiota from stomach acid and bile. Here we show that six commonly used probiotic strains (5 bacteria and 1 yeast) can be encapsulated within CS microspheres. These encapsulated strains survive low pH in vitro for up to 4 hours without appreciable loss in viability as compared to their respective non-encapsulated counterparts. They also survive subsequent exposure to bile. The CS microspheres can be digested by cellulase in levels found in the human intestine, indicating one mechanism of release. Studies in mice that were fed CS encapsulated autofluorescing, commensal E. coli demonstrated release and colonization of the intestinal tract.Conclusion Taken together, the data suggests that CS microencapsulation can protect bacteria and yeasts from viability losses due to stomach acid, allowing the use of lower oral doses of probiotics and microbiota, whilst ensuring good intestinal delivery and release.

scholarly journals Functional Properties of Polyphenols in Grains and Effects of Physicochemical Processing on Polyphenols

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Shuangqi Tian ◽  
Yue Sun ◽  
Zhicheng Chen ◽  
Yingqi Yang ◽  
Yanbo Wang
Keyword(s):  
Phenolic Compounds ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Basic Research ◽  
Whole Grains ◽  
Antioxidant Effect ◽  
Dietary Polyphenols ◽  
Development And Utilization ◽  
Vegetables And Fruits

Phenolic compounds are important products of secondary metabolism in plants. They cannot be synthesized in the human body and are mainly taken from food. Cereals, especially whole grains, are important sources of dietary polyphenols. Compared with vegetables and fruits, the content and biological activities of polyphenols in cereals have long been underestimated. Polyphenols in whole grains are non-nutritive compounds, which are distributed in all structural areas of cereal substances, mainly phenolic acids, flavonoids, and lignans. In recent years, the health effects of whole grains are closely related to their phenolic compounds and their antioxidant activities. Now, different physicochemical processing treatments and their effects have been summarized in order to provide the basis for promoting the development and utilization of food. The various functions of whole grains are closely related to the antioxidant effect of polyphenols. As the basic research on evaluating the antioxidant effect of active substances, in vitro antioxidant tests are faster and more convenient.

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