scholarly journals The Potential of Flavonoids for the Treatment of Neurodegenerative Diseases

2019 ◽  
Vol 20 (12) ◽  
pp. 3056 ◽  
Author(s):  
Pamela Maher
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Biological Activities ◽  
The United States ◽  
Aging Brain ◽  
Disease Development ◽  
Disease Treatment ◽  
Beneficial Effects ◽  
Increased Risk ◽  
Wide Range

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), currently affect more than 6 million people in the United States. Unfortunately, there are no treatments that slow or prevent disease development and progression. Regardless of the underlying cause of the disorder, age is the strongest risk factor for developing these maladies, suggesting that changes that occur in the aging brain put it at increased risk for neurodegenerative disease development. Moreover, since there are a number of different changes that occur in the aging brain, it is unlikely that targeting a single change is going to be effective for disease treatment. Thus, compounds that have multiple biological activities that can impact the various age-associated changes in the brain that contribute to neurodegenerative disease development and progression are needed. The plant-derived flavonoids have a wide range of activities that could make them particularly effective for blocking the age-associated toxicity pathways associated with neurodegenerative diseases. In this review, the evidence for beneficial effects of multiple flavonoids in models of AD, PD, HD, and ALS is presented and common mechanisms of action are identified. Overall, the preclinical data strongly support further investigation of specific flavonoids for the treatment of neurodegenerative diseases.

New Approaches to Profile the Microbiome for Treatment of Neurodegenerative Disease

2021 ◽  
pp. 1-29
Author(s):  
David R. Elmaleh ◽  
Matthew A. Downey ◽  
Ljiljana Kundakovic ◽  
Jeremy E. Wilkinson ◽  
Ziv Neeman ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Gut Microbiome ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Modern Society ◽  
Aging Brain ◽  
New Approaches ◽  
Microbiome Profile ◽  
Carry Over

Progressive neurodegenerative diseases represent some of the largest growing treatment challenges for public health in modern society. These diseases mainly progress due to aging and are driven by microglial surveillance and activation in response to changes occurring in the aging brain. The lack of efficacious treatment options for Alzheimer’s disease (AD), as the focus of this review, and other neurodegenerative disorders has encouraged new approaches to address neuroinflammation for potential treatments. Here we will focus on the increasing evidence that dysbiosis of the gut microbiome is characterized by inflammation that may carry over to the central nervous system and into the brain. Neuroinflammation is the common thread associated with neurodegenerative diseases, but it is yet unknown at what point and how innate immune function turns pathogenic for an individual. This review will address extensive efforts to identify constituents of the gut microbiome and their neuroactive metabolites as a peripheral path to treatment. This approach is still in its infancy in substantive clinical trials and requires thorough human studies to elucidate the metabolic microbiome profile to design appropriate treatment strategies for early stages of neurodegenerative disease. We view that in order to address neurodegenerative mechanisms of the gut, microbiome and metabolite profiles must be determined to pre-screen AD subjects prior to the design of specific, chronic titrations of gut microbiota with low-dose antibiotics. This represents an exciting treatment strategy designed to balance inflammatory microglial involvement in disease progression with an individual’s manifestation of AD as influenced by a coercive inflammatory gut.

scholarly journals An Observational Cohort Study ofClostridium difficileRibotype 027 and Recurrent Infection

mSphere ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Krishna Rao ◽  
Peter D. R. Higgins ◽  
Vincent B. Young
Keyword(s):  
Logistic Regression ◽  
Independent Predictor ◽  
The United States ◽  
Public Health Issue ◽  
Clinical Microbiology Laboratory ◽  
Clinical Predictors ◽  
Content Type ◽  
Ribotype 027 ◽  
Increased Risk ◽  
Wide Range

ABSTRACTRecurrentClostridium difficileinfection (rCDI) frequently complicates recovery from CDI. Accurately predicting rCDI would allow judicious allocation of limited resources, but published models have met with limited success. Thus, biomarkers predictive of recurrence have been sought. This study tested whether PCR ribotype independently predicted rCDI. Stool samples from nonpregnant inpatients ≥18 years of age with diarrhea were included from October 2010 to January 2013 after the patients tested positive forC. difficilein the clinical microbiology laboratory. Per guidelines, the rCDI was defined as a positive test forC. difficileat >2 weeks but ≤8 weeks from the index episode. For each sample, a single colony ofC. difficilewas isolated by anaerobic culture, confirmed to be toxigenic by PCR, and ribotyped. Simple logistic regression and multiple logistic regression were used to model the primary outcome of rCDI, incorporating a wide range of clinical parameters. In total, 927 patients with 968 index episodes of CDI were included, with 110 (11.4%) developing rCDI. Age and use of proton pump inhibitors or concurrent antibiotics did not increase the risk of rCDI. Low serum bilirubin levels and ribotype 027 were associated with increased risk of rCDI on unadjusted analysis, with health care-associated CDI being inversely associated. In the final multivariable model, ribotype 027 was the strongest independent predictor of rCDI (odds ratio, 2.17; 95% confidence interval, 1.33 to 3.56;P= 0.002). Ribotype 027 is an independent predictor of rCDI.IMPORTANCECDI is a major public health issue, with over 400,000 cases per year in the United States alone. Recurrent CDI is common, occurring in approximately one in five individuals after a primary episode. Although interventions exist that could reduce the risk of recurrence, deployment in all patients is limited by cost, invasiveness, and/or an undetermined long-term safety profile. Thus, clinicians need risk stratification tools to properly allocate treatments. Because prior research on clinical predictors has failed to yield a reliable, reproducible, and effective predictive model to assist treatment decisions, accurate biomarkers of recurrence would be of great value. This study tested whether PCR ribotype independently predicted rCDI, and the data build upon prior research in showing that ribotype 027 is associated with rCDI.

scholarly journals Advances in Studies on the Pharmacological Activities of Fucoxanthin

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 634
Author(s):  
Han Xiao ◽  
Jiarui Zhao ◽  
Chang Fang ◽  
Qi Cao ◽  
Maochen Xing ◽  
...  
Keyword(s):  
Biological Activities ◽  
Intestinal Flora ◽  
Small Molecular Weight ◽  
Pharmacological Activities ◽  
Beneficial Effects ◽  
Wide Range ◽  
Cell Components ◽  
Underlying Mechanisms ◽  
Organ Fibrosis ◽  
Active Can

Fucoxanthin is a natural carotenoid derived mostly from many species of marine brown algae. It is characterized by small molecular weight, is chemically active, can be easily oxidized, and has diverse biological activities, thus protecting cell components from ROS. Fucoxanthin inhibits the proliferation of a variety of cancer cells, promotes weight loss, acts as an antioxidant and anti-inflammatory agent, interacts with the intestinal flora to protect intestinal health, prevents organ fibrosis, and exerts a multitude of other beneficial effects. Thus, fucoxanthin has a wide range of applications and broad prospects. This review focuses primarily on the latest progress in research on its pharmacological activity and underlying mechanisms.

scholarly journals Structural Studies of TREM-2 Mutants Linked to Neurodegenerative Diseases

2014 ◽  
Vol 70 (a1) ◽  
pp. C248-C248
Author(s):  
Daniel Kober ◽  
Tom Brett
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Structural Changes ◽  
Expression System ◽  
Point Mutations ◽  
Myeloid Cells ◽  
Surface Protein ◽  
Patient Specific ◽  
Structural Studies ◽  
Increased Risk

Triggering Receptor Expressed on Myeloid Cells-2 (TREM-2) is an extracellular surface protein expressed on myeloid cells of the monocyte/macrophage lineage including dendritic cells, macrophages, osteoclasts, and microglia. Recent genetic studies have revealed point mutations in TREM-2 that correlate with a dramatically increased risk for the development of neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia, and Parkinson's disease. This represents the first molecular link between inflammatory processes and neurodegenerative disease. TREM-2 modulates the innate immune inflammatory response; however, the biological ligand for TREM-2 remains elusive. As a first step towards understanding the role of TREM-2 in neurodegenerative disease, we have undertaken structural and biophysical studies of wild-type and mutant TREM-2 proteins. We developed a mammalian-cell based expression system for the successful production of TREM-2 in quantities suitable for structural studies. We have crystallized the TREM-2 Ig domain and determined the structure at 3.3 Å resolution. Analysis of this structure reveals the location of disease-linked mutations and produces hypotheses about their involvement in structural stability and ligand binding. In addition, we are studying the affect these mutations have on the stability of the protein using biochemical stability and surface expression assays. We are also pursuing structural studies of the point mutants to elucidate any structural changes caused by mutation. These studies are crucial to understanding the functional consequences of TREM-2 point mutations linked to the development of neurodegenerative diseases and, ultimately, to develop patient-specific molecular therapies to treat them.

scholarly journals Caloric restriction: powerful protection for the aging heart and vasculature

2011 ◽  
Vol 301 (4) ◽  
pp. H1205-H1219 ◽  
Author(s):  
Edward P. Weiss ◽  
Luigi Fontana
Keyword(s):  
Arterial Stiffness ◽  
Cardiovascular System ◽  
Current Knowledge ◽  
Left Ventricular Diastolic Function ◽  
The United States ◽  
Left Ventricular ◽  
Cvd Risk ◽  
Beneficial Effects ◽  
Age Related ◽  
Increased Risk

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Research has shown that the majority of the cardiometabolic alterations associated with an increased risk of CVD (e.g., insulin resistance/type 2 diabetes, abdominal obesity, dyslipidemia, hypertension, and inflammation) can be prevented, and even reversed, with the implementation of healthier diets and regular exercise. Data from animal and human studies indicate that more drastic interventions, i.e., calorie restriction with adequate nutrition (CR), may have additional beneficial effects on several metabolic and molecular factors that are modulating cardiovascular aging itself (e.g., cardiac and arterial stiffness and heart rate variability). The purpose of this article is to review the current knowledge on the effects of CR on the aging of the cardiovascular system and CVD risk in rodents, monkeys, and humans. Taken together, research shows that CR has numerous beneficial effects on the aging cardiovascular system, some of which are likely related to reductions in inflammation and oxidative stress. In the vasculature, CR appears to protect against endothelial dysfunction and arterial stiffness and attenuates atherogenesis by improving several cardiometabolic risk factors. In the heart, CR attenuates age-related changes in the myocardium (i.e., CR protects against fibrosis, reduces cardiomyocyte apoptosis, prevents myosin isoform shifts, etc.) and preserves or improves left ventricular diastolic function. These effects, in combination with other benefits of CR, such as protection against obesity, diabetes, hypertension, and cancer, suggest that CR may have a major beneficial effect on health span, life span, and quality of life in humans.

Preparation, Characterization, and In Vitro Evaluation of Resveratrol-Loaded Bovine Serum Album Nanoparticles

2011 ◽  
Vol 345 ◽  
pp. 349-354 ◽  
Author(s):  
Jia Lei Li ◽  
Yuan Gang Zu ◽  
Xiu Hua Zhao ◽  
Dong Mei Zhao ◽  
Xiao Qiang Chen ◽  
...  
Keyword(s):  
Bovine Serum ◽  
Biological Activities ◽  
Cardiovascular Effects ◽  
Entrapment Efficiency ◽  
Cross Linking ◽  
Nano Technology ◽  
Beneficial Effects ◽  
Wide Range

Resveratrol (RES) is a naturally occurring triphenolic phytoalexin compound exerting numerous beneficial effects in the organism. It has a wide range of biological activities in vitro as well as in vivo, such as anti-cancer, antioxidant, anti-inflammatory and beneficial cardiovascular effects. But, its low solubility in water led to its poor absorption in vivo and low bioavailability. Bovine serum album (BSA) nanoparticles have emerged as versatile desired carrier systems due to its ready availability, biodegradability, lack of toxicity and immunogenicity with fast development of nano technology. In this study, RES-BSANPS were prepared by a desolvation method and chemical cross-linking with glutaraldehyde successfully. Results controlled conditions (concentration of BSA, 10 mg/ml; pH = 9.0; volume of ethanol, 6 ml; volume of 0.25 % glutaraldehyde, 100 µl; amount of RES, 6.7 mg; cross-linking time, 24 h at room temperature (1 ml/min)) for entrapment efficiency, loading efficiency, mean particle size and zeta potential, were found to be 88.7 %, 39.4 %, 175.4 ± 0.5 nm, -35.93 ± 0.79 mV, respectively.

scholarly journals Phytochemistry and biological activities of Opuntia seed oils: Opuntia dillenii (Ker Gawl.) Haw. and Opuntia ficus-indica (L.) Mill. A review

2021 ◽  
Vol 67 (2) ◽  
pp. 49-64
Author(s):  
Mohamed Bouhrim ◽  
Saliha Bouknana ◽  
Hayat Ouassou ◽  
Salima Boutahiri ◽  
Nour Elhouda Daoudi ◽  
...  
Keyword(s):  
Arid Regions ◽  
Unsaturated Fatty Acids ◽  
Biological Activities ◽  
The United States ◽  
Biologically Active ◽  
Beneficial Effects ◽  
Set Up ◽  
Phytochemical Studies ◽  
Different Parts ◽  
Opuntia Dillenii

Summary Opuntia species belong to semi-arid and arid regions of Mexico and the United States. O. ficus-indica and O. dillenii are commonly used in alternative medicine to treat various diseases. Up to date, several scientific works have been carried out on the different parts of these plants. However, over the last few years, studies have been focusing on the oil obtained from the fruit seeds of these species. For this reason, this study aims to draw the attention of researchers toward the phytochemical and the pharmacological effects of these two Opuntia oils, which would help set up other scientific projects that promote these products. Phytochemical studies have shown that these oils are rich in biologically active molecules, such as unsaturated fatty acids and phytosterols (mainly linoleic acid and β-sitosterol), as well as vitamin E, which is represented only by the γ-tocopherol. Besides, these oils are rich in polyphenols that protect them from photo-oxidation. Moreover, several studies have shown their antioxidant, anti-diabetic, antibacterial, antifungal, anti-inflammatory, hepatoprotective, and gastroprotective activities, as well as their hypolipidemic properties. The beneficial effects of these oils include also their ability to block the weight loss, and what makes them more interesting is their safety, according to the literature.

The Complexity of Omega-3 Fatty Acid Modulation of Signaling Pathways Related to Pancreatic Cancer

2018 ◽  
Vol 25 (22) ◽  
pp. 2608-2623 ◽  
Author(s):  
Carolina Torres ◽  
Andrew M. Diaz ◽  
Daniel R. Principe ◽  
Paul J. Grippo
Keyword(s):  
Pancreatic Cancer ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Biological Activities ◽  
The United States ◽  
Major Public Health Problem ◽  
Wide Range ◽  
Membrane Structure And Function

Cancer is a major public health problem worldwide and is the second leading cause of death in the United States. Although cancer death rate has dropped by 23% since 1991, there are certain types of cancer for which death rates are still increasing, such as pancreatic cancer. There is an urgent need to find new therapies that could help improve this dreadful outcome. In this regard, the role of nutrition in health and disease has attracted much attention. Several dietary components are involved in metabolic, physiologic and cell signaling affecting tumor growth and progression. Although lipids, and more specifically polyunsaturated fatty acids, have been traditionally studied due to their health effects in cardiovascular disease, it is now clear that they can impact an extensive array of cellular processes that influence a wide range of diseases such as type II diabetes, inflammatory disorders and cancer. These biological activities may be grouped as regulation of: (1) membrane structure and function, (2) intracellular signaling pathways, (3) transcription factor activity, (4) gene expression, and (5) production of bioactive lipid mediators. The aim of this review is to assimilate the current state of knowledge about these potential mechanism(s) of action and signaling pathways modulated by polyunsaturated fatty acids in pancreatic cancer.

Intellectual Development in School-Aged Children With Asymptomatic Congenital Cytomegalovirus Infection

PEDIATRICS ◽  
1986 ◽  
Vol 77 (6) ◽  
pp. 801-806 ◽  
Author(s):  
Thomas J. Conboy ◽  
Robert F. Pass ◽  
Sergio Stagno ◽  
William J. Britt ◽  
Charles A. Alford ◽  
...  
Keyword(s):  
Cytomegalovirus Infection ◽  
Intellectual Development ◽  
The United States ◽  
Congenital Cytomegalovirus Infection ◽  
Congenital Cytomegalovirus ◽  
School Aged Children ◽  
Asymptomatic Children ◽  
Increased Risk ◽  
Wide Range ◽  
Intelligence Scores

Congenital cytomegalovirus infection occurs in about 1% of live births. Although symptomatic congenital infection often results in severe developmental deficits and mental retardation, about 90% have asymtomatic infection. Previous studies of the intellectual development in children with asymptomatic congenital cytomegalovirus have resulted in mixed findings. To control for the effects of hearing impairment (which occurs in about 15% of asymptomatic children) on intelligence scores, we tested 18 prospectively followed, normally hearing, school-aged children with asymptomatic congenital cytomegalovirus (15 black, ten male) and 18 controls matched for age, sex, race, school grade, and socioecnomic status. Children were tested via the Wechsler Intelligence Scale for Children-Revised, the Kaufman Assessment Battery for Children, and the Wide Range Achievement Test. Multivariate analysis revealed no differences between groups on intelligence scores or subscales, achievement scores, or incidence of learning disabilities (defined as significant discrepancy between intelligence and achievement), and mean scores for both groups were very close to national norms. It is concluded that the 25,000 children born in the United States each year with asymptomatic congenital cytomegalovirus and normal hearing are not likely to be at increased risk of mental impairment.

scholarly journals Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies

2018 ◽  
Author(s):  
By Sangeun Park ◽  
Sei-Kyoung Park ◽  
Naruaki Watanabe ◽  
Tadafumi Hashimoto ◽  
Takeshi Iwatsubo ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Chromatin Remodeling ◽  
Mammalian Cells ◽  
Ganglion Cells ◽  
Yeast Prions ◽  
Wide Range ◽  
Associated Proteins ◽  
Lateral Sclerosis

AbstractProteins associated with familial neurodegenerative disease often aggregate in patients’ neurons. Several such proteins, e.g. TDP-43, aggregate and are toxic when expressed in yeast. Deletion of the ATXN2 ortholog, PBP1, reduces yeast TDP-43 toxicity, which led to identification of ATXN2 as an amyotrophic lateral sclerosis (ALS) risk factor and therapeutic target. Likewise, new yeast neurodegenerative disease models could facilitate identification of other risk factors and targets. Mutations in SS18L1, encoding the calcium-responsive transactivator (CREST) chromatin-remodeling protein, are associated with ALS. We show that CREST is toxic in yeast and forms nuclear and occasionally cytoplasmic foci that stain with Thioflavin-T, a dye indicative of amyloid-like protein. Like the yeast chromatin-remodeling factor SWI1, CREST inhibits silencing of FLO genes. Toxicity of CREST is enhanced by the [PIN+] prion and reduced by deletion of the HSP104 chaperone required for the propagation of many yeast prions. Likewise, deletion of PBP1 reduced CREST toxicity and aggregation. In accord with the yeast data, we show that the Drosophila ortholog of human ATXN2, dAtx2, is a potent enhancer of CREST toxicity. Downregulation of dAtx2 in flies overexpressing CREST in retinal ganglion cells was sufficient to largely rescue the severe degenerative phenotype induced by human CREST. Overexpression caused considerable co-localization of CREST and PBP1/ATXN2 in cytoplasmic foci in both yeast and mammalian cells. Thus, co-aggregation of CREST and PBP1/ATXN2 may serve as one of the mechanisms of PBP1/ATXN2-mediated toxicity. These results extend the spectrum of ALS associated proteins whose toxicity is regulated by PBP1/ATXN2, suggesting that therapies targeting ATXN2 may be effective for a wide range of neurodegenerative diseases.Author summaryMutations in the calcium-responsive transactivator (CREST) protein have been shown to cause amyotrophic lateral sclerosis (ALS). Here we show that the human CREST protein expressed in yeast forms largely nuclear aggregates and is toxic. We also show that the HSP104 chaperone required for propagation of yeast prions is likewise required for CREST toxicity. Furthermore deletion of HSP104 affects CREST aggregation. ATXN2, previously shown to modify ALS toxicity caused by mutations in the TDP-43 encoding gene, also modifies toxicity of CREST expressed in either yeast or flies. In addition, deletion of the yeast ATXN2 ortholog reduces CREST aggregation. These results extend the spectrum of ALS associated proteins whose toxicity is regulated by ATXN2, suggesting that therapies targeting ATXN2 may be effective for a wide range of neurodegenerative diseases.

Sign in / Sign up

Export Citation Format

Share Document