Search results for "bioinformatics"

Flanking regions determine the structure of the poly-glutamine homo- repeat in huntingtin through mechanisms common among glutamine-rich human protei…

2020

International audience; The causative agent of Huntington's disease, the poly-Q homo-repeat in the N-terminal region of huntingtin (httex1), is flanked by a 17-residue-long fragment (N17) and a proline-rich region (PRR), which promote and inhibit the aggregation propensity of the protein, respectively, by poorly understood mechanisms. Based on experimental data obtained from site-specifically labeled NMR samples, we derived an ensemble model of httex1 that identified both flanking regions as opposing poly-Q secondary structure promoters. While N17 triggers helicity through a promiscuous hydrogen bond network involving the side chains of the first glutamines in the poly-Q tract, the PRR prom…

Introduction

2014

The cellular, genetic, and hormonal understanding of uterine fibroids is rapidly growing, but the therapeutic options remain similar. Are we really advancing the field?

Metabolomic Analysis of the Effect of Postnatal Hypoxia on the Retina in a Newly Born Piglet Model

2013

The availability of reliable biomarkers of brain injury secondary to birth asphyxia could substantially improve clinical grading, therapeutic intervention strategies, and prognosis. In this study, changes in the metabolome of retinal tissue caused by profound hypoxia in an established neonatal piglet model were investigated using an ultra performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLC-QTOFMS) untargeted metabolomic approach, which included Partial Least Squares - Discriminant Analysis (PLSDA) multivariate data analysis. The initial identification of a set of discriminant metabolites from UPLC-QTOFMS data was confirmed by target UPLC-MS/MS and allowed t…

Translational read-through as an alternative approach for ocular gene therapy of retinal dystrophies caused by in-frame nonsense mutations

2014

AbstractThe eye has become an excellent target for gene therapy, and gene augmentation therapy of inherited retinal disorders has made major progress in recent years. Nevertheless, a recent study indicated that gene augmentation intervention might not stop the progression of retinal degeneration in patients. In addition, for many genes, viral-mediated gene augmentation is currently not feasible due to gene size and limited packaging capacity of viral vectors as well as expression of various heterogeneous isoforms of the target gene. Thus, alternative gene-based strategies to stop or delay the retinal degeneration are necessary. This review focuses on an alternative pharmacologic treatment s…

Efficient gene delivery to photoreceptors using AAV2/rh10 and rescue of the Rho–/– mouse

2015

As gene therapies for various forms of retinal degeneration progress toward human clinical trial, it will be essential to have a repertoire of safe and efficient vectors for gene delivery to the target cells. Recombinant adeno-associated virus (AAV) serotype 2/2 has been shown to be well tolerated in the human retina and has provided efficacy in human patients for some inherited retinal degenerations. In this study, the AAV2/8 and AAV2/rh10 serotypes have been compared as a means of gene delivery to mammalian photoreceptor cells using a photoreceptor specific promoter for transgene expression. Both AAV2/8 and AAV2/rh10 provided rescue of the retinal degeneration present in the rhodopsin kno…

Centenarians maintain miRNA biogenesis pathway while it is impaired in octogenarians.

2016

Centenarians but not octogenarians up regulate the expression of miRNAs, as we previously reported. We have looked into miRNA biogenesis. We show that RNA POL II, DROSHA, EXPORTIN 5 and DICER, are up-regulated in centenarians compared with octogenarians. Furthermore, factors involved in the control of these miRNAs biogenesis genes are also up-regulated in centenarians. Therefore, the up-regulation of miRNA expression in centenarians can be explained in part because miRNA biogenesis pathway is depressed in octogenarians (ordinary aging) while it is maintained in centenarians (extraordinary aging).

Polymorphisms of pro-inflammatory genes and Alzheimer's disease risk: A pharmacogenomic approach.

2006

Clinically and pathologically Alzheimer's disease (AD) represents a sequential progressive neurodegenerative disorder. AD is etiologically heterogeneous and accounts for a majority of dementia in western societies. Inflammation clearly occurs in pathologically vulnerable regions of the AD brain and the search for genetic factors influencing the pathogenesis of AD has lead to the identification of numerous gene polymorphisms that might act as susceptibility modifiers. Accordingly, several reports have indicated that the risk of AD is substantially influenced by several genetic polymorphisms in the promoter region, or other untranslated regions, of genes encoding inflammatory mediators, altho…

Heat Shock Protein-60 and Risk for Cardiovascular Disease

2011

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. There is growing evidence that molecularchaperones, many of which are heat shock proteins HSPs, are involved in CVD pathogenesis. In this review we focus on HSP60,the human mitochondrial chaperone that also displays extramitochondrial and extracellular functions. HSP60 is typically cytoprotectivebut a number of stress conditions determine its conversion to a potentially toxic molecule for cells and tissues. We present illustrative examplesof specific subtypes of CVD where HSP60 is implicated in the initiation and/or progression of disease. The data not only indicatea pathogenic role for HSP60 but also its …

Resistin: a new marker of cardiorenal risk?

2010

Von der symptomatischen zur kausalen Therapie?

2009

Until today the pharmacological therapy of Alzheimer’s disease (AD) is still limited to symptomatic temporary improvement or stabilization of cognitive performance and activities of daily living, and the reduction of neuropsychiatric symptoms of the disease. Available symptomatic treatment options are the acetylcholinesterase inhibitors (ACh-I) donepezil, galantamine, rivastigmine, and the partial N-Methyl-D-Aspartat-(NMDA)-antagonist memantine. Further substances with symptomatic targets, especially selective acetylcholine and histamine receptors, are currently under development. Numerous of disease-modifying substances mainly targeting components of the amyloidogenic pathway of AD are pre…