Common therapeutic strategies for prion and Alzheimer’s diseases

2016 ◽  
Vol 397 (11) ◽  
pp. 1115-1124 ◽  
Author(s):  
Saioa R. Elezgarai ◽  
Emiliano Biasini
Keyword(s):  
Protein Synthesis ◽  
Therapeutic Strategies ◽  
Cellular Prion Protein ◽  
Protein Isoforms ◽  
Therapeutic Interventions ◽  
Misfolded Protein ◽  
The Past ◽  
Protein Synthesis Machinery ◽  
Alzheimer’S Diseases ◽  
Alzheimer's Diseases

Abstract A number of unexpected pathophysiological connections linking different neurodegenerative diseases have emerged over the past decade. An example is provided by prion and Alzheimer’s diseases. Despite being distinct pathologies, these disorders share several neurotoxic mechanisms, including accumulation of misfolded protein isoforms, stress of the protein synthesis machinery, and activation of a neurotoxic signaling mediated by the cellular prion protein. Here, in addition to reviewing these mechanisms, we will discuss the potential therapeutic interventions for prion and Alzheimer’s diseases that are arising from the comprehension of their common neurodegenerative pathways.

scholarly journals Mechanistic studies of non-canonical amino acid mutagenesis

2021 ◽  
Author(s):  
Rachel C. Fleisher ◽  
Nina Michael ◽  
Ruben L Gonzalez
Keyword(s):  
Protein Synthesis ◽  
Single Molecule ◽  
Cellular Protein ◽  
Full Potential ◽  
Mechanistic Studies ◽  
The Past ◽  
The Poor ◽  
Protein Synthesis Machinery ◽  
Canonical Amino Acid ◽  
Amino Acid Mutagenesis

Over the past decade, harnessing the cellular protein synthesis machinery to incorporate non-canonical amino acids (ncAAs) into tailor-made peptides has significantly advanced many aspects of molecular science. More recently, groundbreaking progress in our ability to engineer this machinery for improved ncAA incorporation has led to significant enhancements of this powerful tool for biology and chemistry. By revealing the molecular basis for the poor or improved incorporation of ncAAs, mechanistic studies of ncAA incorporation by the protein synthesis machinery have tremendous potential for informing and directing such engineering efforts. In this chapter, we describe a set of complementary biochemical and single-molecule fluorescence assays that we have adapted for mechanistic studies of ncAA incorporation. Collectively, these assays provide data that can guide engineering of the protein synthesis machinery to expand the range of ncAAs that can be incorporated into peptides and increase the efficiency with which they can be incorporated, thereby enabling the full potential of ncAA mutagenesis technology to be realized.

scholarly journals Mitochondria-Targeted Protective Compounds in Parkinson’s and Alzheimer’s Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-30 ◽  
Author(s):  
Carlos Fernández-Moriano ◽  
Elena González-Burgos ◽  
M. Pilar Gómez-Serranillos
Keyword(s):  
Mitochondrial Dysfunction ◽  
Therapeutic Strategies ◽  
Nervous System Diseases ◽  
Central Nervous System Diseases ◽  
Cellular Energy ◽  
Alzheimer’S Diseases ◽  
Atp Regulation ◽  
Alzheimer's Diseases

Mitochondria are cytoplasmic organelles that regulate both metabolic and apoptotic signaling pathways; their most highlighted functions include cellular energy generation in the form of adenosine triphosphate (ATP), regulation of cellular calcium homeostasis, balance between ROS production and detoxification, mediation of apoptosis cell death, and synthesis and metabolism of various key molecules. Consistent evidence suggests that mitochondrial failure is associated with early events in the pathogenesis of ageing-related neurodegenerative disorders including Parkinson’s disease and Alzheimer’s disease. Mitochondria-targeted protective compounds that prevent or minimize mitochondrial dysfunction constitute potential therapeutic strategies in the prevention and treatment of these central nervous system diseases. This paper provides an overview of the involvement of mitochondrial dysfunction in Parkinson’s and Alzheimer’s diseases, with particular attention toin vitroandin vivostudies on promising endogenous and exogenous mitochondria-targeted protective compounds.

Strategies for the Treatment of Acute Promyelocytic Leukemia

2006 ◽  
Vol 4 (1) ◽  
pp. 37-50 ◽  
Author(s):  
Olga Frankfurt ◽  
Martin S. Tallman
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Therapeutic Strategies ◽  
Promyelocytic Leukemia ◽  
Therapeutic Interventions ◽  
The Past

The outcome of acute promyelocytic leukemia (APL) has improved dramatically during the past 40 years. Insights into the genetic and biologic mechanisms of APL lead to the development of specific and effective therapeutic strategies. This article discusses the therapeutic interventions that transformed APL from one of the most lethal leukemias to one that is highly curable.

Truth Matters: Cognitive Integrity as an Intervention for Self-Deception

2017 ◽  
Author(s):  
Eugenia Isabel Gorlin ◽  
Michael W. Otto
Keyword(s):  
Decision Making ◽  
Problem Solving ◽  
Autonomous Agents ◽  
Therapeutic Interventions ◽  
Empirical Validation ◽  
The Past ◽  
Adaptive Problem

To live well in the present, we take direction from the past. Yet, individuals may engage in a variety of behaviors that distort their past and current circumstances, reducing the likelihood of adaptive problem solving and decision making. In this article, we attend to self-deception as one such class of behaviors. Drawing upon research showing both the maladaptive consequences and self-perpetuating nature of self-deception, we propose that self-deception is an understudied risk and maintaining factor for psychopathology, and we introduce a “cognitive-integrity”-based approach that may hold promise for increasing the reach and effectiveness of our existing therapeutic interventions. Pending empirical validation of this theoretically-informed approach, we posit that patients may become more informed and autonomous agents in their own therapeutic growth by becoming more honest with themselves.

scholarly journals Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation

Cell ◽  
2021 ◽  
Vol 184 (9) ◽  
pp. 2520
Author(s):  
Joseph Tcherkezian ◽  
Perry A. Brittis ◽  
Franziska Thomas ◽  
Philippe P. Roux ◽  
John G. Flanagan
Keyword(s):  
Protein Synthesis ◽  
Protein Synthesis Machinery

scholarly journals NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xuan Wang ◽  
Jun Cai ◽  
Lei Zhao ◽  
Dejun Zhang ◽  
Guojie Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Bioinformatics Analysis ◽  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
Self Renewal ◽  
Tumor Relapse ◽  
The Past ◽  
Overwhelming Evidence ◽  
Novel Therapeutic Strategies

AbstractExperimental and clinical studies over the past two decades have provided overwhelming evidence that human cancers, including prostate cancer (PCa), harbor cancer stem cells (CSCs) that sustain tumor growth, drive tumor progression and mediate therapy resistance and tumor relapse. Recent studies have also implicated NUMB as a PCa suppressor and an inhibitor of PCa stem cells (PCSCs); however, exactly how NUMB functions in these contexts remains unclear. Here, by employing bioinformatics analysis and luciferase assays and by conducting rescue experiments, we first show that NUMB is directly targeted by microRNA-9-5p (miR-9-5p), an oncogenic miR associated with poor prognosis in many malignancies. We further show that miR-9-5p levels are inversely correlated with NUMB expression in CD44+ PCSCs. miR-9-5p reduced NUMB expression and inhibited numerous PCSC properties including proliferation, migration, invasion as well as self-renewal. Strikingly, overexpression of NUMB in CD44+ PCSCs overcame all of the above PCSC properties enforced by miR-9-5p. Taken together, our results suggest that inhibiting the expression of the oncomiR miR-9-5p and overexpressing NUMB may represent novel therapeutic strategies to target PCSCs and PCa metastasis.

scholarly journals Gut Microbiota and NAFLD: Pathogenetic Mechanisms, Microbiota Signatures, and Therapeutic Interventions

2021 ◽  
Vol 9 (5) ◽  
pp. 957
Author(s):  
Tomas Hrncir ◽  
Lucia Hrncirova ◽  
Miloslav Kverka ◽  
Robert Hromadka ◽  
Vladimira Machova ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Therapeutic Strategies ◽  
Therapeutic Interventions ◽  
Faecal Microbiota ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Immunological Mechanisms ◽  
Major Factors ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Its worldwide prevalence is rapidly increasing and is currently estimated at 24%. NAFLD is highly associated with many features of the metabolic syndrome, including obesity, insulin resistance, hyperlipidaemia, and hypertension. The pathogenesis of NAFLD is complex and not fully understood, but there is increasing evidence that the gut microbiota is strongly implicated in the development of NAFLD. In this review, we discuss the major factors that induce dysbiosis of the gut microbiota and disrupt intestinal permeability, as well as possible mechanisms leading to the development of NAFLD. We also discuss the most consistent NAFLD-associated gut microbiota signatures and immunological mechanisms involved in maintaining the gut barrier and liver tolerance to gut-derived factors. Gut-derived factors, including microbial, dietary, and host-derived factors involved in NAFLD pathogenesis, are discussed in detail. Finally, we review currently available diagnostic and prognostic methods, summarise latest knowledge on promising microbiota-based biomarkers, and discuss therapeutic strategies to manipulate the microbiota, including faecal microbiota transplantation, probiotics and prebiotics, deletions of individual strains with bacteriophages, and blocking the production of harmful metabolites.

scholarly journals Therapeutic Strategies for Diabetic Kidney Disease

Diabetology ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 31-35
Author(s):  
Keiichiro Matoba
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Intensive Therapy ◽  
Therapeutic Strategies ◽  
Therapeutic Interventions ◽  
Hemodynamic Changes ◽  
Diabetic Kidney ◽  
Global Epidemic ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is a global epidemic leading to end-stage renal disease (ESRD) and susceptibility to cardiovascular disease, with few therapeutic interventions. A hallmark of DKD is the activation of the renin-angiotensin-aldosterone system and hemodynamic changes in glomerulus. Although intensive therapy with agents that targets those abnormalities lowers the risk of DKD progression, it does not completely abolish the risk of ESRD and cardiovascular events. Recent studies have illustrated the importance of renal inflammation, oxidative stress, and activated Rho-associated protein kinase (ROCK) signaling as essential pathogenesis for the development of DKD. In this commentary, these topics will be discussed.

scholarly journals Sphingolipid lysosomal storage diseases: from bench to bedside

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Muna Abed Rabbo ◽  
Yara Khodour ◽  
Laurie S. Kaguni ◽  
Johnny Stiban
Keyword(s):  
Basic Research ◽  
Lysosomal Storage Diseases ◽  
Therapeutic Strategies ◽  
Clinical Applications ◽  
Late Nineteenth Century ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
The Past ◽  
Health And Disease ◽  
General Aspects

AbstractJohann Ludwig Wilhelm Thudicum described sphingolipids (SLs) in the late nineteenth century, but it was only in the past fifty years that SL research surged in importance and applicability. Currently, sphingolipids and their metabolism are hotly debated topics in various biochemical fields. Similar to other macromolecular reactions, SL metabolism has important implications in health and disease in most cells. A plethora of SL-related genetic ailments has been described. Defects in SL catabolism can cause the accumulation of SLs, leading to many types of lysosomal storage diseases (LSDs) collectively called sphingolipidoses. These diseases mainly impact the neuronal and immune systems, but other systems can be affected as well. This review aims to present a comprehensive, up-to-date picture of the rapidly growing field of sphingolipid LSDs, their etiology, pathology, and potential therapeutic strategies. We first describe LSDs biochemically and briefly discuss their catabolism, followed by general aspects of the major diseases such as Gaucher, Krabbe, Fabry, and Farber among others. We conclude with an overview of the available and potential future therapies for many of the diseases. We strive to present the most important and recent findings from basic research and clinical applications, and to provide a valuable source for understanding these disorders.

scholarly journals Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xudong Zhu ◽  
Zhiyang Chen ◽  
Weiyan Shen ◽  
Gang Huang ◽  
John M. Sedivy ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cellular Response ◽  
State Of The Art ◽  
Cell Senescence ◽  
Therapeutic Interventions ◽  
Cell Fate Decision ◽  
The Past ◽  
Fate Decision ◽  
The Individual ◽  
Remarkable Progress

AbstractRemarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ageing. Epigenetic dynamics and immunometabolic reprogramming link to the alterations of cellular response to intrinsic and extrinsic stimuli, representing current hotspots as they not only (re-)shape the individual cell identity, but also involve in cell fate decision. This review focuses on the present findings and emerging concepts in epigenetic, inflammatory, and metabolic regulations and the consequences of the ageing process. Potential therapeutic interventions targeting cell senescence and regulatory mechanisms, using state-of-the-art techniques are also discussed.

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