Redefining neuroprotective gene therapeutic strategies: Lessons learned from caloric restriction and NAD+ metabolism

2005 ◽  
Vol 6 (s6) ◽  
pp. S43-S46
Author(s):  
L.A. Henricksen ◽  
H.J. Federoff
Keyword(s):  
Caloric Restriction ◽  
Therapeutic Strategies ◽  
Lessons Learned ◽  
Nad Metabolism

Organic- or Inorganic-based Nanomaterials: Opportunities and Challenges in the Selection for Biomedicine

2021 ◽  
Vol 27 ◽  
Author(s):  
Ranjith Kankala
Keyword(s):  
Chemical Composition ◽  
Physicochemical Properties ◽  
Surface Area ◽  
Therapeutic Strategies ◽  
Lessons Learned ◽  
Clinical Translation ◽  
Significant Progress ◽  
Morphological Attributes ◽  
The Past ◽  
Selection For

: Since the inception of nanotechnology, several efforts have been dedicated to fabricating diverse nanodevices with exceptional performance. These innovative constructs have been applied in medicine due to their tailorable physicochemical properties (chemical composition, optical activity, spectra, and charge) and morphological attributes (size, shape, and surface area). Moreover, these versatile nanomedicines could promisingly offer better performance over the conventional therapeutic strategies. Broadly speaking, in terms of chemical composition, nanobiomaterials are classified into two predominant categories of organic and inorganic-based components. Despite their success and enormous versatile advancements in the past two decades, the significant progress towards clinical translation has been hampered by their corresponding intrinsic limitations. In this perspective, we give a brief overview of these organic- and inorganic-based materials, highlighting opportunities and challenges towards their utilization in medicine. Finally, we provide an interesting outlook in lessons learned and looking forward to developing these materials, emphasizing their scope towards clinical translation.

scholarly journals Identification of evolutionary and kinetic drivers of NAD-dependent signaling

2019 ◽  
Vol 116 (32) ◽  
pp. 15957-15966 ◽  
Author(s):  
Mathias Bockwoldt ◽  
Dorothée Houry ◽  
Marc Niere ◽  
Toni I. Gossmann ◽  
Ines Reinartz ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Phylogenetic Analyses ◽  
Adenosine Diphosphate ◽  
Therapeutic Strategies ◽  
Structural Adaptation ◽  
Disease Treatment ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Nad Metabolism ◽  
High Affinity ◽  
Cellular Events

Nicotinamide adenine dinucleotide (NAD) provides an important link between metabolism and signal transduction and has emerged as central hub between bioenergetics and all major cellular events. NAD-dependent signaling (e.g., by sirtuins and poly–adenosine diphosphate [ADP] ribose polymerases [PARPs]) consumes considerable amounts of NAD. To maintain physiological functions, NAD consumption and biosynthesis need to be carefully balanced. Using extensive phylogenetic analyses, mathematical modeling of NAD metabolism, and experimental verification, we show that the diversification of NAD-dependent signaling in vertebrates depended on 3 critical evolutionary events: 1) the transition of NAD biosynthesis to exclusive usage of nicotinamide phosphoribosyltransferase (NamPT); 2) the occurrence of nicotinamide N-methyltransferase (NNMT), which diverts nicotinamide (Nam) from recycling into NAD, preventing Nam accumulation and inhibition of NAD-dependent signaling reactions; and 3) structural adaptation of NamPT, providing an unusually high affinity toward Nam, necessary to maintain NAD levels. Our results reveal an unexpected coevolution and kinetic interplay between NNMT and NamPT that enables extensive NAD signaling. This has implications for therapeutic strategies of NAD supplementation and the use of NNMT or NamPT inhibitors in disease treatment.

scholarly journals Taking the Myc out of cancer: toward therapeutic strategies to directly inhibit c-Myc

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Sarah K. Madden ◽  
Aline Dantas de Araujo ◽  
Mara Gerhardt ◽  
David P. Fairlie ◽  
Jody M. Mason
Keyword(s):  
Transcription Factor ◽  
Side Effects ◽  
Therapeutic Strategy ◽  
Tumor Regression ◽  
Therapeutic Strategies ◽  
Lessons Learned ◽  
Direct Inhibition ◽  
Human Cancers ◽  
E Box

Abstractc-Myc is a transcription factor that is constitutively and aberrantly expressed in over 70% of human cancers. Its direct inhibition has been shown to trigger rapid tumor regression in mice with only mild and fully reversible side effects, suggesting this to be a viable therapeutic strategy. Here we reassess the challenges of directly targeting c-Myc, evaluate lessons learned from current inhibitors, and explore how future strategies such as miniaturisation of Omomyc and targeting E-box binding could facilitate translation of c-Myc inhibitors into the clinic.

scholarly journals Evolution of Natural Lifespan Variation and Molecular Strategies of Extended Lifespan

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 32-33
Author(s):  
Alaattin Kaya
Keyword(s):  
Caloric Restriction ◽  
Genetic Basis ◽  
Epigenetic Landscape ◽  
Intermediary Metabolites ◽  
Replicative Lifespan ◽  
Nad Metabolism ◽  
Wild Yeast ◽  
Lifespan Variation ◽  
Extended Lifespan ◽  
Selective Forces

Abstract To understand the genetic basis and the selective forces acting on longevity, it is useful to employ ecologically diverse individuals of the same species, widely different in lifespan. This way, we may capture the experiment of Nature that modifies the genotype arriving at different lifespans. Here, we analyzed 76 ecologically diverse wild yeast isolates and discovered wide diversity of lifespan. We sequenced the genomes of these organisms and analyzed how their replicative lifespan is shaped by nutrients and transcriptional and metabolite patterns. By identifying genes, proteins and metabolites that correlate with longevity across these isolates, we found that long-lived strains elevate intermediary metabolites, differentially regulate genes involved in NAD metabolism and adjust control of epigenetic landscape through conserved, rare histone modifier. Our data further offer insights into the evolution and mechanisms by which caloric restriction regulates lifespan by modulating the availability of nutrients without decreasing fitness.

scholarly journals Therapeutic Potential of Emerging NAD+-Increasing Strategies for Cardiovascular Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1939
Author(s):  
Noemi Rotllan ◽  
Mercedes Camacho ◽  
Mireia Tondo ◽  
Elena M. G. Diarte-Añazco ◽  
Marina Canyelles ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Nicotinamide Adenine Dinucleotide ◽  
Therapeutic Potential ◽  
Metabolic Stress ◽  
Therapeutic Strategies ◽  
Experimental Models ◽  
Vascular Health ◽  
Nad Metabolism ◽  
Pathological Conditions ◽  
Mammalian Tissues

Cardiovascular diseases are the leading cause of death worldwide. Aging and/or metabolic stress directly impact the cardiovascular system. Over the last few years, the contributions of altered nicotinamide adenine dinucleotide (NAD+) metabolism to aging and other pathological conditions closely related to cardiovascular diseases have been intensively investigated. NAD+ bioavailability decreases with age and cardiometabolic conditions in several mammalian tissues. Compelling data suggest that declining tissue NAD+ is commonly related to mitochondrial dysfunction and might be considered as a therapeutic target. Thus, NAD+ replenishment by either genetic or natural dietary NAD+-increasing strategies has been recently demonstrated to be effective for improving the pathophysiology of cardiac and vascular health in different experimental models, as well as human health, to a lesser extent. Here, we review and discuss recent experimental evidence illustrating that increasing NAD+ bioavailability, particularly by the use of natural NAD+ precursors, may offer hope for new therapeutic strategies to prevent and treat cardiovascular diseases.

scholarly journals NAPRT Expression Regulation Mechanisms: Novel Functions Predicted by a Bioinformatics Approach

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 2022
Author(s):  
Sara Duarte-Pereira ◽  
Olga Fajarda ◽  
Sérgio Matos ◽  
José Luís Oliveira ◽  
Raquel Monteiro Silva
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
High Energy ◽  
Therapeutic Strategies ◽  
Main Role ◽  
Cancer Therapies ◽  
Nad Metabolism ◽  
Extracellular Form ◽  
Regulation Mechanisms

The nicotinate phosphoribosyltransferase (NAPRT) gene has gained relevance in the research of cancer therapeutic strategies due to its main role as a NAD biosynthetic enzyme. NAD metabolism is an attractive target for the development of anti-cancer therapies, given the high energy requirements of proliferating cancer cells and NAD-dependent signaling. A few studies have shown that NAPRT expression varies in different cancer types, making it imperative to assess NAPRT expression and functionality status prior to the application of therapeutic strategies targeting NAD. In addition, the recent finding of NAPRT extracellular form (eNAPRT) suggested the involvement of NAPRT in inflammation and signaling. However, the mechanisms regulating NAPRT gene expression have never been thoroughly addressed. In this study, we searched for NAPRT gene expression regulatory mechanisms in transcription factors (TFs), RNA binding proteins (RBPs) and microRNA (miRNAs) databases. We identified several potential regulators of NAPRT transcription activation, downregulation and alternative splicing and performed GO and expression analyses. The results of the functional analysis of TFs, RBPs and miRNAs suggest new, unexpected functions for the NAPRT gene in cell differentiation, development and neuronal biology.

scholarly journals Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Panagiotis F. Christopoulos ◽  
Torleif T. Gjølberg ◽  
Stig Krüger ◽  
Guttorm Haraldsen ◽  
Jan Terje Andersen ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Inflammatory Diseases ◽  
Notch Signaling Pathway ◽  
Therapeutic Strategies ◽  
Lessons Learned ◽  
Chronic Inflammatory Diseases ◽  
Cell Fate Decisions ◽  
The Impact

The Notch signaling pathway regulates developmental cell-fate decisions and has recently also been linked to inflammatory diseases. Although therapies targeting Notch signaling in inflammation in theory are attractive, their design and implementation have proven difficult, at least partly due to the broad involvement of Notch signaling in regenerative and homeostatic processes. In this review, we summarize the supporting role of Notch signaling in various inflammation-driven diseases, and highlight efforts to intervene with this pathway by targeting Notch ligands and/or receptors with distinct therapeutic strategies, including antibody designs. We discuss this in light of lessons learned from Notch targeting in cancer treatment. Finally, we elaborate on the impact of individual Notch members in inflammation, which may lay the foundation for development of therapeutic strategies in chronic inflammatory diseases.

Lessons Learned From Coaching Postsecondary Students With Traumatic Brain Injury

2020 ◽  
Vol 5 (1) ◽  
pp. 88-96
Author(s):  
Mary R. T. Kennedy
Keyword(s):  
College Students ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sense Of Self ◽  
Scientific Evidence ◽  
Sudden Onset ◽  
Lessons Learned ◽  
Speech Language Pathologists ◽  
The Brain ◽  
Exhaustive List

Purpose The purpose of this clinical focus article is to provide speech-language pathologists with a brief update of the evidence that provides possible explanations for our experiences while coaching college students with traumatic brain injury (TBI). Method The narrative text provides readers with lessons we learned as speech-language pathologists functioning as cognitive coaches to college students with TBI. This is not meant to be an exhaustive list, but rather to consider the recent scientific evidence that will help our understanding of how best to coach these college students. Conclusion Four lessons are described. Lesson 1 focuses on the value of self-reported responses to surveys, questionnaires, and interviews. Lesson 2 addresses the use of immediate/proximal goals as leverage for students to update their sense of self and how their abilities and disabilities may alter their more distal goals. Lesson 3 reminds us that teamwork is necessary to address the complex issues facing these students, which include their developmental stage, the sudden onset of trauma to the brain, and having to navigate going to college with a TBI. Lesson 4 focuses on the need for college students with TBI to learn how to self-advocate with instructors, family, and peers.

Experiences With and Lessons Learned From Developing, Implementing, and Evaluating a Support Program for Older Hearing Aid Users and Their Communication Partners in the Hearing Aid Dispensing Setting

2020 ◽  
Vol 29 (3S) ◽  
pp. 638-647 ◽  
Author(s):  
Janine F. J. Meijerink ◽  
Marieke Pronk ◽  
Sophia E. Kramer
Keyword(s):  
Large Scale ◽  
Hearing Aid ◽  
Critical Discussion ◽  
Lessons Learned ◽  
Research Note ◽  
Support Program ◽  
Large Sample Size ◽  
Long Term Effects ◽  
Communication Program ◽  
Communication Partners

Purpose The SUpport PRogram (SUPR) study was carried out in the context of a private academic partnership and is the first study to evaluate the long-term effects of a communication program (SUPR) for older hearing aid users and their communication partners on a large scale in a hearing aid dispensing setting. The purpose of this research note is to reflect on the lessons that we learned during the different development, implementation, and evaluation phases of the SUPR project. Procedure This research note describes the procedures that were followed during the different phases of the SUPR project and provides a critical discussion to describe the strengths and weaknesses of the approach taken. Conclusion This research note might provide researchers and intervention developers with useful insights as to how aural rehabilitation interventions, such as the SUPR, can be developed by incorporating the needs of the different stakeholders, evaluated by using a robust research design (including a large sample size and a longer term follow-up assessment), and implemented widely by collaborating with a private partner (hearing aid dispensing practice chain).

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