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PubMed Journals Articles About "Gene Study Yields Possible Alzheimer Target" RSS

21:08 EDT 20th September 2019 | BioPortfolio

Gene Study Yields Possible Alzheimer Target PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Gene Study Yields Possible Alzheimer Target articles that have been published worldwide.

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Showing "Gene Study Yields Possible Alzheimer Target" PubMed Articles 1–25 of 74,000+

Targeting apolipoprotein E for treating Alzheimer's disease.

The ε4 allele of the apolipoprotein E gene represents the most widely reproduced and robust susceptibility loci for the most common late onset and sporadic forms of Alzheimer's disease. While the discovery of this now widely replicated association was reported more than 25 years ago, few therapeutic interventions that specifically target the apolipoprotein pathway in brain have emerged. Here we discuss our current understanding of apolipoprotein E biology in brain, its relationship to the pathogenesis of A...


Mental Disorders in Young Adults from Families with the Presenilin-1 Gene Mutation E280A in the Preclinical Stage of Alzheimer's Disease.

There are forms of Alzheimer's disease (AD) that have an autosomal dominant inheritance pattern; one of them is caused by the E280A mutation in the gene that codes for Presenilin-1 (PSEN1). Studying families of people with this mutation allows the evaluation of characteristics of the subjects before cognitive decline begins.

Transcriptional Dysregulation Study Reveals a Core Network Involving the Progression of Alzheimer's Disease.

The pathogenesis of Alzheimer's disease is associated with dysregulation at different levels from transcriptome to cellular functioning. Such complexity necessitates investigations of disease etiology to be carried out considering multiple aspects of the disease and the use of independent strategies. The established works more emphasized on the structural organization of gene regulatory network while neglecting the internal regulation changes. Applying a strategy different from popularly used co-expression...


PAX7 target gene repression is a superior FSHD biomarker than DUX4 target gene activation, associating with pathological severity and identifying FSHD at the single-cell level.

Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable skeletal myopathy. The condition is linked to hypomethylation of the D4Z4 macrosatellite repeat at chromosome 4q35, leading to epigenetic derepression of the transcription factor DUX4; coupled with a permissive 4qA haplotype supplying a poly(A) signal. DUX4 may drive FSHD pathology via both induction of target genes and inhibition of the function of the myogenic master regulator PAX7. Biomarkers for FSHD have focused on DUX4 target gene...

Drug repurposing for Alzheimer's disease based on transcriptional profiling of human iPSC-derived cortical neurons.

Alzheimer's disease is a complex disorder encompassing multiple pathological features with associated genetic and molecular culprits. However, target-based therapeutic strategies have so far proved ineffective. The aim of this study is to develop a methodology harnessing the transcriptional changes associated with Alzheimer's disease to develop a high content quantitative disease phenotype that can be used to repurpose existing drugs. Firstly, the Alzheimer's disease gene expression landscape covering sever...

Characterization of the binding of tau imaging ligands to melanin-containing cells: putative off-target-binding site.

Amyloid-β plaques and neurofibrillary tangles composed of tau protein are the neuropathological hallmarks of Alzheimer's disease. In recent years, marked progress has been made in Alzheimer's disease research using tau ligands for positron emission tomography (PET). However, the issue of off-target binding, that is, the binding of ligands to regions without tau pathology, remains unresolved. Tissues with melanin-containing cells (MCCs) have been suggested as binding targets for tau ligands. In the present ...

Off-target genome editing: a new discipline of gene science and a new of class medicine.

With an increasing growth of genome editing, off-target effects such as non-specific genetic modifications resulting from the designed process of genome editing become a new discipline of gene science and new class medicine. The degree of short-term and long-term side effects and toxicity or dynamics of the primary and secondary off-target genome editing varies with the application of different methodologies of gene editing and measuring, readouts of genetic modifications, or comparison reference. Measureme...

Genetic factors associated with the predisposition to late onset Alzheimer's disease.

Alzheimer's disease is a progressive, irreversible neurodegenerative disorder characterized by loss of memory and cognitive skills. More than 90% of cases are sporadic and have later age of onset. Many studies have shown a genetic predisposition for late onset Alzheimer's disease (LOAD). The most studied genetic predisposition factor is apolipoprotein E gene besides other susceptibility genes involved in vascular pathologies, homocysteine metabolism, and neuronal growth and differentiation such as methylene...

IsomiRs: Expanding the miRNA repression toolbox beyond the seed.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that play increasingly appreciated roles in gene regulation. In animals, miRNAs silence gene expression by binding to partially complementary sequences within target mRNAs. It is well-established that miRNAs recognize canonical target sites by base-pairing in the 5'region. However, the development of biochemical methods has identified many novel, non-canonical target sites, suggesting additional modes of miRNA-target association. Here, we review the cu...

DiCre-Based Inducible Disruption of Leishmania Genes.

Conditional gene deletion using dimerizable Cre recombinase (DiCre) is so far the best developed system for the phenotypic analysis of essential genes in Leishmania species. Here, we describe a protocol for the generation of a conditional gene deletion mutant and the subsequent inducible deletion of a target gene. Leishmania parasites are genetically modified to express two inactive Cre subunits (DiCre) and a single LoxP-flanked version of a target gene in a context where both endogenous copies of the gene ...

Adeno-associated virus-based Alzheimer's disease mouse models and potential new therapeutic avenues.

Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that presents with cognitive decline. The current understanding of underlying disease mechanisms remains incomplete. Genetically modified mouse models have been instrumental in deciphering pathomechanisms in AD. While these models were typically generated by classical transgenesis and genome editing, the use of adeno-associated viruses (AAVs) to model and investigate AD in mice, as well as to develop novel gene-therapy approaches are...

A pilot study of exenatide actions in Alzheimer's disease.

Strong preclinical evidence suggests that exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist used for treating type 2 diabetes, is neuroprotective and disease- modifying in Alzheimer's disease (AD).

MicroRNA target gene prediction of ischemic stroke by using variational Bayesian inference for Gauss mixture model.

MicroRNAs (miRNAs) as biomarkers of numerous diseases, are a novel group of single-stranded, non-coding small RNA molecules, which can regulate the gene expression and transcription or translation of target genes. Therefore, accurately identifying miRNAs and predicting their potential target genes correlated with ischemic stroke contribute to quick understanding and diagnosis of the pathogenesis of ischemic stroke. In order to identify the targets of miRNAs, the differential expression and expression profil...

Identification of 20(R, S)-protopanaxadiol and 20(R, S)-protopanaxatriol for potential selective modulation of glucocorticoid receptor.

Although glucocorticoids (GCs) are widely used as anti-inflammatory drugs, they are often accompanied by adverse effects, which are mainly due to the transactivation of glucocorticoid receptor (GR) target genes. In order to screen novel plant-derived GR ligands (phytocorticoids) capable of separating transrepression from transactivation, this work focuses on the estimation of 20(R, S)-protopanaxadiol [PPD(R, S)] and 20(R, S)-protopanaxatriol [PPT(R, S)] for their dissociated characteristics. The reporter ge...

Visualizing modules of coordinated structural brain atrophy during the course of conversion to Alzheimer's disease by applying methodology from gene co-expression analysis.

We aimed to identify modularized structural atrophy of brain regions with a high degree of connectivity and its longitudinal changes associated with the progression of Alzheimer's disease (AD) using weighted gene co-expression network analysis (WGCNA), which is an unsupervised hierarchical clustering method originally used in genetic analysis.

Pharmacological Targets and the Biological Mechanisms of Formononetin for Alzheimer's Disease: A Network Analysis.

BACKGROUND This study aimed to identify the pharmacological targets and mechanisms of action of the traditional Chinese medicine, formononetin, in the treatment of Alzheimer's disease (AD) using network pharmacological analysis. MATERIAL AND METHODS Targets of AD were obtained by using DisGeNET gene discovery platform, the herbal ingredients target (HIT) database, the SuperPred, and the SwissTargetPrediction compound target prediction platforms. Pathogenic and therapeutic targets were imported to the STRING...

Novel multi target-directed ligands targeting 5-HT receptors with in cellulo antioxidant properties as promising leads in Alzheimer's disease.

Facing the complexity of Alzheimer's disease (AD), it is now currently admitted that a therapeutic pleiotropic intervention is needed to alter its progression. Among the major hallmarks of the disease, the amyloid pathology and the oxidative stress are closely related. We propose in this study to develop original Multi-Target Directed Ligands (MTDL) able to impact at the same time Aβ protein accumulation and toxicity of Reactive Oxygen Species (ROS) in neuronal cells. Such MTDL were obtained by linking on ...

Multi-target 1,4-dihydropyridines showing calcium channel blockade and antioxidant capacity for Alzheimer's disease therapy.

In this work we describe the synthesis, Ca channel blockade capacity and antioxidant power of N,N-bis(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,6-dimethyl-4-aryl-1,4-dihydropyridine-3,5-dicarboxamides 1-9, a number of multi-target small 1,4-dihydropyridines (DHP), designed by juxtaposition of melatonin and nimodipine. As a result, we have identified antioxidant DHP 7 (Ca channel blockade: 55%, and 8.78 Trolox/Equivalents), the most balanced DHP analyzed here, for potential Alzheimer's disease therapy.

Association between rs10046, rs1143704, rs767199, rs727479, rs1065778, rs1062033, rs1008805, and rs700519 polymorphisms in aromatase (CYP19A1) gene and Alzheimer's disease risk: a systematic review and meta-analysis involving 11,051 subjects.

CYP19A1 enzyme (aromatase) encoded by CYP19A1 (cytochrome p450 family 19 subfamily a member 1) gene plays a key role in the biosynthesis of estrogen, which has been significantly associated with Alzheimer's disease (AD). To ascertain whether CYP19A1 gene polymorphisms are correlated with the susceptibility to AD, we performed this systematic review and meta-analysis of currently available studies.

The correlation between mammalian target of rapamycin (mTOR) gene expression and sperm DNA damage among infertile patients with and without varicocele.

This study aimed to assess the possible correlation between mammalian target of rapamycin (mTOR) gene expression and sperm DNA damage among infertile patients with and without varicocele. The study included sixty infertile males and fifty fertile males as controls. The infertile group was subdivided into the following subgroups: thirty males with varicocele and thirty males without varicocele. All subjects underwent medical history collection, clinical examination, semen analysis, sperm DNA integrity assess...

Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality.

Gene transfer has long been a compelling yet elusive therapeutic modality. First mainly considered for rare inherited disorders, gene therapy may open treatment opportunities for more challenging and complex diseases such as Alzheimer's or Parkinson's disease. Today, examples of striking clinical proof of concept, the first gene therapy drugs coming onto the market, and the emergence of powerful new molecular tools have broadened the number of avenues to target neurological disorders but have also highlight...

A 48-Week, Multicenter, Open-Label, Observational Study Evaluating Oral Rivastigmine in Patients with Mild-to-Moderate Alzheimer's Disease in Taiwan.

Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer's type. This study assessed the short- and long-term effectiveness and safety of rivastigmine in patients with mild-to-moderate Alzheimer's disease (AD) in a real-world clinical setting in Taiwan.

Synthesis and biological evaluation of flavone-8-acrylamide derivatives as potential multi-target-directed anti Alzheimer agents and investigation of binding mechanism with acetylcholinesterase.

In a search for novel multifunctional anti-Alzheimer agents, a congeneric set of seventeen flavone-8-acrylamide derivatives (8a─q) were synthesized and evaluated for their cholinesterase inhibitory, antioxidant, neuroprotective and modulation of Aβ aggregation activities. The target compounds showed effective and selective inhibitory activity against the AChE over BuChE. In addition, the target compounds also showed moderate anti-oxidant activity and strong neuroprotective capacities, and accelerated dos...

Trihalomethane yields from twelve aromatic halogenated disinfection byproducts during chlor(am)ination.

As the first identified category of disinfection byproducts (DBPs), trihalomethanes (THMs) have received continuous attention. Previous studies have demonstrated that the transformation of aromatic halogenated DBPs during chlor (am)ination resulted in the formation of THMs, which may occur in both water treatment plants and drinking water distribution systems. In this study, THM yields from aromatic chlorinated/brominated DBPs during chlorination and aromatic iodinated DBPs during chloramination were invest...

Advancement of multi-target drug discoveries and promising applications in the field of Alzheimer's disease.

Complex diseases (e.g., Alzheimer's disease) or infectious diseases are usually caused by complicated and varied factors, including environmental and genetic factors. Multi-target (polypharmacology) drugs have been suggested and have emerged as powerful and promising alternative paradigms in modern medicinal chemistry for the development of versatile chemotherapeutic agents to solve these medical challenges. The multifunctional agents capable of modulating multiple biological targets simultaneously display ...


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