scholarly journals PRPS-Associated Disorders and the Drosophila Model of Arts Syndrome

2020 ◽  
Vol 21 (14) ◽  
pp. 4824
Author(s):  
Keemo Delos Santos ◽  
Eunjeong Kwon ◽  
Nam-Sung Moon
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Fruit Fly ◽  
Nucleotide Metabolism ◽  
Human Diseases ◽  
Past Century ◽  
Missense Mutations ◽  
Phosphoribosyl Pyrophosphate ◽  
Potential Applications ◽  
Short Palindromic Repeat

While a plethora of genetic techniques have been developed over the past century, modifying specific sequences of the fruit fly genome has been a difficult, if not impossible task. clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 truly redefined molecular genetics and provided new tools to model human diseases in Drosophila melanogaster. This is particularly true for genes whose protein sequences are highly conserved. Phosphoribosyl pyrophosphate synthetase (PRPS) is a rate-limiting enzyme in nucleotide metabolism whose missense mutations are found in several neurological disorders, including Arts syndrome. In addition, PRPS is deregulated in cancer, particularly those that become resistant to cancer therapy. Notably, Drosophila PRPS shares about 90% protein sequence identity with its human orthologs, making it an ideal gene to study via CRISPR/Cas9. In this review, we will summarize recent findings on PRPS mutations in human diseases including cancer and on the molecular mechanisms by which PRPS activity is regulated. We will also discuss potential applications of Drosophila CRISPR/Cas9 to model PRPS-dependent disorders and other metabolic diseases that are associated with nucleotide metabolism.

scholarly journals Drosophila melanogaster: A Veritable Genetic Tool and in vivo Model for Human Alzheimer’s Disease

2019 ◽  
pp. 1-9
Author(s):  
Oluwatosin Imoleayo, Oyeniran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drosophila Melanogaster ◽  
Molecular Mechanisms ◽  
Fruit Fly ◽  
Human Diseases ◽  
Model Organisms ◽  
In Vivo Model ◽  
Brain Functions ◽  
Drosophila Models

The rise in the cases of neurodegenerative diseases, such as the familial forms of Alzheimer’s disease is worrisome and a burden to many societies in our ever-increasing world. Due to the complexity in the nature of the brain and spinal cord characterized by an extremely organized network of neuronal cells, there is a need to answer scientific inquiries in uncomplicated, though similar, systems. Drosophila melanogaster (fruit-fly) is a well-studied and easily managed genetic model organism used for discerning the molecular mechanisms of many human diseases. There are strong conservations of several basic biological, physiological and neurological features between D. melanogaster and mammals, as about 75% of all human disease-causing genes are considered to possess a functional homolog in the fruit-fly. The development of Drosophila models of several neurodegenerative disorders via developed transgenic technologies has presented spectacular similarities to human diseases. An advantage that the fruit-fly has over other model organisms, such as the mouse, is its comparatively brief lifespan, which allows complex inquiries about brain functions to be addressed more quickly. Furthermore, there have been steady increases in understanding the pathophysiological basis of many neurological disorders via genetic screenings with the aid of Drosophila models. This review presents a widespread summary of the fruit-fly models relevant to Alzheimer’s disease, and highlight important genetic modifiers that have been recognized using this model.

scholarly journals Integrative Metabolomics to Identify Molecular Signatures of Responses to Vaccines and Infections

Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 492
Author(s):  
Joann Diray-Arce ◽  
Maria Giulia Conti ◽  
Boryana Petrova ◽  
Naama Kanarek ◽  
Asimenia Angelidou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Nucleotide Metabolism ◽  
Human Immune System ◽  
Innate And Adaptive Immunity ◽  
Health And Disease ◽  
Human Immune ◽  
Fresh Insight ◽  
Insight Into

Approaches to the identification of metabolites have progressed from early biochemical pathway evaluation to modern high-dimensional metabolomics, a powerful tool to identify and characterize biomarkers of health and disease. In addition to its relevance to classic metabolic diseases, metabolomics has been key to the emergence of immunometabolism, an important area of study, as leukocytes generate and are impacted by key metabolites important to innate and adaptive immunity. Herein, we discuss the metabolomic signatures and pathways perturbed by the activation of the human immune system during infection and vaccination. For example, infection induces changes in lipid (e.g., free fatty acids, sphingolipids, and lysophosphatidylcholines) and amino acid pathways (e.g., tryptophan, serine, and threonine), while vaccination can trigger changes in carbohydrate and bile acid pathways. Amino acid, carbohydrate, lipid, and nucleotide metabolism is relevant to immunity and is perturbed by both infections and vaccinations. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying the host immune response. Its integration with other systems biology platforms will enhance studies of human health and disease.

scholarly journals Patient-derived phosphoribosyl pyrophosphate synthetase mutations in Drosophila result in autophagy and lysosome dysfunction

2018 ◽  
Author(s):  
Keemo Delos Santos ◽  
Christine Yergeau ◽  
Nam-Sung Moon
Keyword(s):  
Oxidative Stress ◽  
Neurological Disorders ◽  
Cellular Response ◽  
Nucleotide Metabolism ◽  
Nutrient Deprivation ◽  
Missense Mutations ◽  
Phosphoribosyl Pyrophosphate ◽  
Autophagy Induction ◽  
Rate Limiting ◽  
Phosphoribosyl Pyrophosphate Synthetase

AbstractPhosphoribosyl pyrophosphate synthetase (PRPS) is a rate-limiting enzyme in nucleotide metabolism. While missense mutations of PRPS1 have been identified in neurological disorders such as Arts syndrome, little is known on how they contribute to pathogenesis. We engineered Drosophila PRPS (dPRPS) alleles that carry patient-derived PRPS missense mutations. Although dPRPS mutant flies develop normally, they have profound defects in autophagy induction and lysosome function. Consequently, dPRPS flies are sensitive to nutrient deprivation as they are unable to break down lipid storage by macroautophagy. In addition, we provide evidence showing that dRPPS is required for proper cellular response to oxidative stress, providing a possible mechanism by which PRPS1 dysfunction contributes to neurological disorders.

scholarly journals Checking NEKs: Overcoming a Bottleneck in Human Diseases

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1778 ◽  
Author(s):  
Andressa Peres de Oliveira ◽  
Luidy Kazuo Issayama ◽  
Isadora Carolina Betim Pavan ◽  
Fernando Riback Silva ◽  
Talita Diniz Melo-Hanchuk ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Human Diseases ◽  
Therapeutic Approaches ◽  
Cellular Processes ◽  
Extracellular Signal ◽  
Damage Response ◽  
Cilia Formation ◽  
Potential Applications ◽  
Phosphoinositide 3 Kinase

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as the cell cycle, cell division, cilia formation, and the DNA damage response. The review of the literature points to the pivotal participation of NEKs in important human diseases, like different types of cancer, diabetes, ciliopathies and central nervous system related and inflammatory-related diseases. The different known regulatory molecular mechanisms specific to each NEK are also presented, relating to their involvement in different diseases. In addition, important information about NEKs remains to be elucidated and is highlighted in this review, showing the need for other studies and research regarding this kinase family. Therefore, the NEK family represents an important group of kinases with potential applications in the therapy of human diseases.

tiRNAs & tRFs Biogenesis and Regulation of Diseases: A Review

2019 ◽  
Vol 26 (31) ◽  
pp. 5849-5861 ◽  
Author(s):  
Pan Jiang ◽  
Feng Yan
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Metabolic Diseases ◽  
Viral Infections ◽  
Regulatory Mechanisms ◽  
Biological Functions ◽  
Reverse Transcriptases ◽  
Dna Damage Responses ◽  
Potential Applications ◽  
Viral Reverse Transcriptases

tiRNAs & tRFs are a class of small molecular noncoding tRNA derived from precise processing of mature or precursor tRNAs. Most tiRNAs & tRFs described originate from nucleus-encoded tRNAs, and only a few tiRNAs and tRFs have been reported. They have been suggested to play important roles in inhibiting protein synthesis, regulating gene expression, priming viral reverse transcriptases, and the modulation of DNA damage responses. However, the regulatory mechanisms and potential function of tiRNAs & tRFs remain poorly understood. This review aims to describe tiRNAs & tRFs, including their structure, biological functions and subcellular localization. The regulatory roles of tiRNAs & tRFs in translation, neurodegeneration, metabolic diseases, viral infections, and carcinogenesis are also discussed in detail. Finally, the potential applications of these noncoding tRNAs as biomarkers and gene regulators in different diseases is also highlighted.

Periodontal Pathogens and Neuropsychiatric Health

2020 ◽  
Vol 20 (15) ◽  
pp. 1353-1397 ◽  
Author(s):  
Abhishek Wadhawan ◽  
Mark A. Reynolds ◽  
Hina Makkar ◽  
Alison J. Scott ◽  
Eileen Potocki ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Low Grade ◽  
Periodontal Pathogens ◽  
Synergistic Interactions ◽  
Brain Vasculature ◽  
Micro Rnas ◽  
Clinical Conditions ◽  
Low Grade Inflammation ◽  
Neuropsychiatric Illness

Increasing evidence incriminates low-grade inflammation in cardiovascular, metabolic diseases, and neuropsychiatric clinical conditions, all important causes of morbidity and mortality. One of the upstream and modifiable precipitants and perpetrators of inflammation is chronic periodontitis, a polymicrobial infection with Porphyromonas gingivalis (P. gingivalis) playing a central role in the disease pathogenesis. We review the association between P. gingivalis and cardiovascular, metabolic, and neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation as well as downregulation induced by the pathogen. In addition to inflammation, translocation of the pathogens to the coronary and peripheral arteries, including brain vasculature, and gut and liver vasculature has important pathophysiological consequences. Distant effects via translocation rely on virulence factors of P. gingivalis such as gingipains, on its synergistic interactions with other pathogens, and on its capability to manipulate the immune system via several mechanisms, including its capacity to induce production of immune-downregulating micro-RNAs. Possible targets for intervention and drug development to manage distal consequences of infection with P. gingivalis are also reviewed.

scholarly journals Nanocomposite scaffolds for accelerating chronic wound healing by enhancing angiogenesis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hamed Nosrati ◽  
Reza Aramideh Khouy ◽  
Ali Nosrati ◽  
Mohammad Khodaei ◽  
Mehdi Banitalebi-Dehkordi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Wound Healing ◽  
Tissue Regeneration ◽  
Molecular Mechanisms ◽  
Healing Process ◽  
The Body ◽  
Key Factors ◽  
Potential Applications ◽  
Nanocomposite Scaffolds

AbstractSkin is the body’s first barrier against external pathogens that maintains the homeostasis of the body. Any serious damage to the skin could have an impact on human health and quality of life. Tissue engineering aims to improve the quality of damaged tissue regeneration. One of the most effective treatments for skin tissue regeneration is to improve angiogenesis during the healing period. Over the last decade, there has been an impressive growth of new potential applications for nanobiomaterials in tissue engineering. Various approaches have been developed to improve the rate and quality of the healing process using angiogenic nanomaterials. In this review, we focused on molecular mechanisms and key factors in angiogenesis, the role of nanobiomaterials in angiogenesis, and scaffold-based tissue engineering approaches for accelerated wound healing based on improved angiogenesis.

scholarly journals Modeling Gastrointestinal Diseases Using Organoids to Understand Healing and Regenerative Processes

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1331
Author(s):  
Alexane Ollivier ◽  
Maxime M. Mahe ◽  
Géraldine Guasch
Keyword(s):  
Molecular Mechanisms ◽  
Gastrointestinal Disease ◽  
3D Culture ◽  
Gastrointestinal Diseases ◽  
Continuous Series ◽  
Regenerative Therapy ◽  
Disease Mechanisms ◽  
Epithelial Wound Healing ◽  
Potential Applications

The gastrointestinal tract is a continuous series of organs from the mouth to the esophagus, stomach, intestine and anus that allows digestion to occur. These organs are frequently associated with chronic stress and injury during life, subjecting these tissues to frequent regeneration and to the risk of developing disease-associated cancers. The possibility of generating human 3D culture systems, named organoids, that resemble histologically and functionally specific organs, has opened up potential applications in the analysis of the cellular and molecular mechanisms involved in epithelial wound healing and regenerative therapy. Here, we review how during normal development homeostasis takes place, and the role of the microenvironmental niche cells in the intestinal stem cell crypt as an example. Then, we introduce the notion of a perturbed niche during disease conditions affecting the esophageal–stomach junction and the colon, and describe the potential applications of organoid models in the analysis of human gastrointestinal disease mechanisms. Finally, we highlight the perspectives of organoid-based regenerative therapy to improve the repair of the epithelial barrier.

scholarly journals Proanthocyanidins against Oxidative Stress: From Molecular Mechanisms to Clinical Applications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lingyu Yang ◽  
Dehai Xian ◽  
Xia Xiong ◽  
Rui Lai ◽  
Jing Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Low Cost ◽  
Natural Agents ◽  
Molecular Damage ◽  
And Control

Proanthocyanidins (PCs) are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerousin vitroandin vivostudies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, anti-inflammation, immunomodulation, DNA repair, and antitumor activity. Accumulation of prooxidants such as reactive oxygen species (ROS) exceeding cellular antioxidant capacity results in oxidative stress (OS), which can damage macromolecules (DNA, lipids, and proteins), organelles (membranes and mitochondria), and whole tissues. OS is implicated in the pathogenesis and exacerbation of many cardiovascular, neurodegenerative, dermatological, and metabolic diseases, both through direct molecular damage and secondary activation of stress-associated signaling pathways. PCs are promising natural agents to safely prevent acute damage and control chronic diseases at relatively low cost. In this review, we summarize the molecules and signaling pathways involved in OS and the corresponding therapeutic mechanisms of PCs.

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