scholarly journals Methylxanthines and Neurodegenerative Diseases: An Update

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 803
Author(s):  
Daniel Janitschke ◽  
Anna A. Lauer ◽  
Cornel M. Bachmann ◽  
Heike S. Grimm ◽  
Tobias Hartmann ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Lipid Homeostasis ◽  
Phosphodiesterase Inhibition ◽  
Neuroprotective Effects ◽  
The Past ◽  
Naturally Occurring ◽  
Interesting Approach ◽  
The Impact

Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed in food, several synthetic but also non-synthetic methylxanthines are used as pharmaceuticals, in particular in treating airway constrictions. Besides the well-established bronchoprotective effects, methylxanthines are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid homeostasis and have neuroprotective effects. Known molecular mechanisms include adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation and gene regulation. By affecting several pathways associated with neurodegenerative diseases via different pleiotropic mechanisms and due to its moderate side effects, intake of methylxanthines have been suggested to be an interesting approach in dealing with neurodegeneration. Especially in the past years, the impact of methylxanthines in neurodegenerative diseases has been extensively studied and several new aspects have been elucidated. In this review we summarize the findings of methylxanthines linked to Alzheimer´s disease, Parkinson’s disease and Multiple Sclerosis since 2017, focusing on epidemiological and clinical studies and addressing the underlying molecular mechanisms in cell culture experiments and animal studies in order to assess the neuroprotective potential of methylxanthines in these diseases.

Animal Models of Neurodegenerative Diseases

2016 ◽  
Author(s):  
David Baglietto-Vargas ◽  
Rahasson R. Ager ◽  
Rodrigo Medeiros ◽  
Frank M. LaFerla
Keyword(s):  
Animal Models ◽  
Life Expectancy ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Preclinical Studies ◽  
Pathological Features ◽  
The Past ◽  
The Brain

The incidence and prevalence of neurodegenerative disorders (e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), etc.) are growing rapidly due to increasing life expectancy. Researchers over the past two decades have focused their efforts on the development of animal models to dissect the molecular mechanisms underlying neurodegenerative disorders. Existing models, however, do not fully replicate the symptomatic and pathological features of human diseases. This chapter focuses on animal models of AD, as this disorder is the most prevalent of the brain degenerative conditions afflicting society. In particular, it briefly discusses the current leading animal models, the translational relevance of the preclinical studies using such models, and the limitations and shortcomings of using animals to model human disease. It concludes with a discussion of potential means to improve future models to better recapitulate human conditions.

Neuroscience of Pediatric PTSD

2017 ◽  
Author(s):  
Victor G. Carrión ◽  
Carl F. Weems
Keyword(s):  
Mental Health Professionals ◽  
Traumatic Stress ◽  
Emotional Processing ◽  
Animal Studies ◽  
Stress Disorder ◽  
Sleep Regulation ◽  
The Past ◽  
Broad Array ◽  
Work Done ◽  
The Impact

The overarching goal of Neuroscience of Pediatric PTSD is to provide mental health professionals and students with a review of the broad array of research related to the neurobiology of developmental traumatic stress. In doing so, it attempts to provide a synthesis of how this body of work has built a foundation from which we can launch new ways of studying the impact of trauma in children and adolescents. It uses posttraumatic stress disorder (PTSD) as an anchor to inform on these advancements. The past 20 years have seen an increased interest in how traumatic stress impacts development. Neuroscience of Pediatric PTSD summarizes key work done in areas pertinent to function and development. It discusses advances in the neuroscience of executive function, memory, emotional processing, and associated features such as dissociation, self-injurious behaviors, and sleep regulation. Each chapter is divided in three parts: animal studies, adult studies, and child studies. Issues such as comorbidity and treatment, and their relationship to these neuroscience findings, are presented.

scholarly journals Tumor Cells and Cancer-Associated Fibroblasts: An Updated Metabolic Perspective

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 399
Author(s):  
Géraldine Gentric ◽  
Fatima Mechta-Grigoriou
Keyword(s):  
Tumor Cells ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Carbon Sources ◽  
Cancer Associated Fibroblasts ◽  
The Past ◽  
Cancer Field ◽  
Metabolic Heterogeneity ◽  
The Impact ◽  
Shed Light

During the past decades, metabolism and redox imbalance have gained considerable attention in the cancer field. In addition to the well-known Warburg effect occurring in tumor cells, numerous other metabolic deregulations have now been reported. Indeed, metabolic reprograming in cancer is much more heterogeneous than initially thought. In particular, a high diversity of carbon sources used by tumor cells has now been shown to contribute to this metabolic heterogeneity in cancer. Moreover, the molecular mechanisms newly highlighted are multiple and shed light on novel actors. Furthermore, the impact of this metabolic heterogeneity on tumor microenvironment has also been an intense subject of research recently. Here, we will describe the new metabolic pathways newly uncovered in tumor cells. We will also have a particular focus on Cancer-Associated Fibroblasts (CAF), whose identity, function and metabolism have been recently under profound investigation. In that sense, we will discuss about the metabolic crosstalk between tumor cells and CAF.

scholarly journals Sex Differences of the Diabetic Heart

2021 ◽  
Vol 12 ◽  
Author(s):  
Natacha Fourny ◽  
Christophe Beauloye ◽  
Monique Bernard ◽  
Sandrine Horman ◽  
Martine Desrois ◽  
...  
Keyword(s):  
Sex Differences ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Vascular Complications ◽  
Clinical Findings ◽  
Personalized Care ◽  
Increased Risk ◽  
Treatment Of Diabetes ◽  
The Impact

Type 2 diabetes is a chronic disease associated with micro- and macro-vascular complications, including myocardial ischemia, and also with a specific and intrinsic cardiac dysfunction called diabetic cardiomyopathy (DCM). Both clinical and animal studies demonstrate significant sex differences in prevalence, pathophysiology, and outcomes of cardiovascular diseases (CVDs), including those associated with diabetes. The increased risk of CVDs with diabetes is higher in women compared to men with 50% higher risk of coronary artery diseases and increased mortality when exposed to acute myocardial infarction. Clinical studies also reveal a sexual dimorphism in the incidence and outcomes of DCM. Based on these clinical findings, growing experimental research was initiated to understand the impact of sex on CVDs associated with diabetes and to identify the molecular mechanisms involved. Endothelial dysfunction, atherosclerosis, coagulation, and fibrosis are mechanisms found to be sex-differentially modulated in the diabetic cardiovascular system. Recently, impairment of energy metabolism also emerged as a determinant of multiple CVDs associated with diabetes. Therefore, future studies should thoroughly analyze the sex-specific metabolic determinants to propose new therapeutic targets. With current medicine tending toward more personalized care of patients, we finally propose to discuss the importance of sex as determinant in the treatment of diabetes-associated cardiac diseases to promote a more systemic inclusion of both males and females in clinical and preclinical studies.

scholarly journals A Proteomic Approach to Uncover Neuroprotective Mechanisms of Oleocanthal against Oxidative Stress

2018 ◽  
Vol 19 (8) ◽  
pp. 2329 ◽  
Author(s):  
Laura Giusti ◽  
Cristina Angeloni ◽  
Maria Barbalace ◽  
Serena Lacerenza ◽  
Federica Ciregia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Olive Oil ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
Neuroprotective Effects ◽  
Proteomic Approach ◽  
Mitochondrial Functions

Neurodegenerative diseases represent a heterogeneous group of disorders that share common features like abnormal protein aggregation, perturbed Ca2+ homeostasis, excitotoxicity, impairment of mitochondrial functions, apoptosis, inflammation, and oxidative stress. Despite recent advances in the research of biomarkers, early diagnosis, and pharmacotherapy, there are no treatments that can halt the progression of these age-associated neurodegenerative diseases. Numerous epidemiological studies indicate that long-term intake of a Mediterranean diet, characterized by a high consumption of extra virgin olive oil, correlates with better cognition in aged populations. Olive oil phenolic compounds have been demonstrated to have different biological activities like antioxidant, antithrombotic, and anti-inflammatory activities. Oleocanthal, a phenolic component of extra virgin olive oil, is getting more and more scientific attention due to its interesting biological activities. The aim of this research was to characterize the neuroprotective effects of oleocanthal against H2O2-induced oxidative stress in neuron-like SH-SY5Y cells. Moreover, protein expression profiling, combined with pathways analyses, was used to investigate the molecular events related to the protective effects. Oleocanthal was demonstrated to counteract oxidative stress, increasing cell viability, reducing reactive oxygen species (ROS) production, and increasing reduced glutathione (GSH) intracellular level. Proteomic analysis revealed that oleocanthal significantly modulates 19 proteins in the presence of H2O2. In particular, oleocanthal up-regulated proteins related to the proteasome, the chaperone heat shock protein 90, the glycolytic enzyme pyruvate kinase, and the antioxidant enzyme peroxiredoxin 1. Moreover, oleocanthal protection seems to be mediated by Akt activation. These data offer new insights into the molecular mechanisms behind oleocanthal protection against oxidative stress.

scholarly journals The impact of epigenetics on the development of neurodegenerative diseases

2021 ◽  
Author(s):  
Gustavo Hugo de Souza Faria
Keyword(s):  
Dna Methylation ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Disease Onset ◽  
Specific Protein ◽  
Aberrant Methylation ◽  
Transcriptional Dysregulation ◽  
Altered Gene ◽  
The Impact

Introduction: Neurodegenerative diseases affect thousands of people in Brazil and have been increasing in frequency with the aging population. However, little is known about the molecular mechanisms and biomarkers of these diseases, which leads to a medical approach based on symptomatic and unresolving characteristics. Epigenetics, including DNA methylation, histone modifications, and changes in regulatory RNAs, emerges as a tool for prevention of neurodegenerative diseases. Objectives: To review studies that discuss the role of epigenetics in the development of neurodegenerative diseases. Methodology: This study involved an integrative review of papers published from 2016 to 2021 by searching PubMed and Scopus. Results: The studies showed that there is evidence that epigenetic mechanisms interfere with the development of major neurodegenerative diseases. Huntington’s disease presents an altered gene from birth, but transcriptional dysregulation is characteristic of the pathology that may be correlated to the age of disease onset in the cortex. In Parkinson’s disease dysregulation of expression of a specific protein is believed to play a central role in the disease and occurs through aberrant methylation that controls activation or suppression. In relation to Alzheimer’s disease, it has been found that deregulated DNA methylation and demethylation is linked to the onset and progression of the disease. In addition, these epigenetic factors are interfered with by diet, aging, and exercise. Conclusions: Investment in epigenetic studies is needed to understand possible markers of neurodegenerative diseases, for early diagnosis and the formation of epidrugs with the ability to treat.

Mitochondrial dysfunction plays a key role in the development of neurodegenerative diseases in diabetes

2020 ◽  
Vol 318 (5) ◽  
pp. E750-E764 ◽  
Author(s):  
Han Cheng ◽  
Xiaokun Gang ◽  
Yujia Liu ◽  
Gang Wang ◽  
Xue Zhao ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Reactive Oxygen Species Generation ◽  
Hypoglycemic Agents ◽  
Neuroprotective Effects ◽  
Mitochondrial Dysfunctions ◽  
Dipeptidyl Peptidase 4 ◽  
Beneficial Effects ◽  
Glucagon Like Peptide 1

Mitochondria have an essential function in cell survival due to their role in bioenergetics, reactive oxygen species generation, calcium buffering, and other metabolic activities. Mitochondrial dysfunctions are commonly found in neurodegenerative diseases (NDs), and diabetes is a risk factor for NDs. However, the role of mitochondria in diabetic neurodegeneration is still unclear. In the present study, we review the latest evidence on the role of mitochondrial dysfunctions in the development of diabetes-related NDs and the underlying molecular mechanisms. Hypoglycemic agents, especially metformin, have been proven to have neuroprotective effects in the treatment of diabetes, in which mitochondria could act as one of the underlying mechanisms. Other hypoglycemic agents, including thiazolidinediones (TZDs), dipeptidyl peptidase 4 (DPP-4) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists, have gained more attention because of their beneficial effects on NDs, presumably by improving mitochondrial function. Our review highlights the notion that mitochondria could be a promising therapeutic target in the treatment of NDs in patients with diabetes.

scholarly journals Relevance of Autophagy and Mitophagy Dynamics and Markers in Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 149
Author(s):  
Carlotta Giorgi ◽  
Esmaa Bouhamida ◽  
Alberto Danese ◽  
Maurizio Previati ◽  
Paolo Pinton ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Neural Cells ◽  
Innovative Strategy ◽  
The Past ◽  
Specialized Form ◽  
Intracellular Aggregates ◽  
Potential Biomarkers

During the past few decades, considerable efforts have been made to discover and validate new molecular mechanisms and biomarkers of neurodegenerative diseases. Recent discoveries have demonstrated how autophagy and its specialized form mitophagy are extensively associated with the development, maintenance, and progression of several neurodegenerative diseases. These mechanisms play a pivotal role in the homeostasis of neural cells and are responsible for the clearance of intracellular aggregates and misfolded proteins and the turnover of organelles, in particular, mitochondria. In this review, we summarize recent advances describing the importance of autophagy and mitophagy in neurodegenerative diseases, with particular attention given to multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. We also review how elements involved in autophagy and mitophagy may represent potential biomarkers for these common neurodegenerative diseases. Finally, we examine the possibility that the modulation of autophagic and mitophagic mechanisms may be an innovative strategy for overcoming neurodegenerative conditions. A deeper knowledge of autophagic and mitophagic mechanisms could facilitate diagnosis and prognostication as well as accelerate the development of therapeutic strategies for neurodegenerative diseases.

scholarly journals Neuroprotective Effects of Taraxacum officinale Wigg. Extract on Glutamate-Induced Oxidative Stress in HT22 Cells via HO-1/Nrf2 Pathways

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 926 ◽  
Author(s):  
Shan Huang ◽  
Ning Meng ◽  
Zhiming Liu ◽  
Li Guo ◽  
Linsha Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Taraxacum Officinale ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Neuroprotective Effects ◽  
Ht22 Cells

Oxidative stress-mediated neuron damage is considered an important contributor to the pathogenesis and development of neurodegenerative diseases. Taraxacum officinale has been reported to possess antioxidant activities. However, whether it can protect neurons against oxidative damage and the underlying molecular mechanisms have not been fully determined. In the present study, we examined the neuroprotective effects of ethanol extracts of this plant (ETOW) on glutamate-induced oxidative stress in HT22 cells. Both cell viability and reactive oxygen species (ROS) assays showed that ETOW effectively attenuated glutamate-induced cytotoxicity and ROS generation. Furthermore, our results revealed that ETOW increased the expression of heme oxygenase-1 (HO-1) and promoted the nuclear translocation of nuclear factor erythroid 2-related factor-2 (Nrf2). The inhibitory effects of ETOW on glutamate-stimulated cell toxicity and ROS production were partially reversed by tin protoporphyrin (SnPP), an HO activity inhibitor. Taken together, these results demonstrate that ETOW can protect HT22 cells against glutamate-induced oxidative damage by inducing the Nrf2/HO-1 pathways. Our study supports the idea that Taraxacum officinale Wigg. is a promising agent for preventing neurodegenerative diseases.

scholarly journals Molecular Transducers of Physical Activity Consortium (MoTrPAC) Progress and Study Protocol Design

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1757-1757
Author(s):  
Lyndon Joseph ◽  
Williams John
Keyword(s):  
Physical Activity ◽  
Study Protocol ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Protocol Design ◽  
Treadmill Running ◽  
Beneficial Effects ◽  
Public Data ◽  
Response To Exercise ◽  
The Impact

Abstract Objectives Physical activity is beneficial to human health and wellbeing across the lifespan. The numerous benefits of regular physical activity (PA) have long been recognized. Despite this, most exercise studies are associational and the molecular mechanisms that are the bases for the beneficial effects remain obscure as are the mechanisms of multiorgan communications and benefits. MoTrPAC is a large NIH discovery project (19 grants; 37 Principal Investigators; 23 institutions) whose goals are to assemble a comprehensive map of the molecular changes that occur in response to exercise and provide insights into how they are altered by age, sex, body composition and fitness level and develop a user-friendly database to facilitate investigator-initiated studies and catalyze the field of PA research and explore hypotheses exploring novel mechanisms by which PA improves or preserves health. Methods This project will explore and document changes in molecules mobilized in blood, muscle and fat in humans as well as 15 additional tissues for rats in response to different aerobic and resistance exercise regimes. The human studies are a multicenter clinical trial cohort of people of both sexes from 10–80 years of age and recruitment has begun. Preclinical animal Studies (PASS) have been conducted in 6 and 18-month old F344 rats and tissues harvested from control inactive rats and rats at seven time-points following a single 30 minute acute bout of treadmill running. A separate group of rats were subjected to an intensive (70% VO2max) and progressive run training program of 5 day/week for 1,2, 4, or 8 weeks with 18 tissues collected. Multiple state of art and omics platforms including genomic, transcriptomic, epigenomic, proteomic and metabolomics are being employed to define and discover the molecules mobilized in response to exercise. Results This presentation will highlight the study protocol design and data from the initial public data release (November 15th, 2019). Data will be available to the extramural community to collaborate with the MoTrPAC investigators to explore innovative mechanisms to expand the impact of the initial studies. Conclusions The product from this consortium will begin to characterize the molecular mechanisms of molecules identified in the ‘molecular map’ that underlie the beneficial effects of PA. Funding Sources National Institutes of Health.

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