Search results for "P46"
showing 10 items of 12 documents
Cholesterol Hydroxylating Cytochrome P450 46A1: From Mechanisms of Action to Clinical Applications
2021
Cholesterol, an essential component of the brain, and its local metabolism are involved in many neurodegenerative diseases. The blood-brain barrier is impermeable to cholesterol; hence, cholesterol homeostasis in the central nervous system represents a balance betweenin situbiosynthesis and elimination. Cytochrome P450 46A1 (CYP46A1), a central nervous system-specific enzyme, converts cholesterol to 24-hydroxycholesterol, which can freely cross the blood-brain barrier and be degraded in the liver. By the dual action of initiating cholesterol efflux and activating the cholesterol synthesis pathway, CYP46A1 is the key enzyme that ensures brain cholesterol turnover. In humans and mouse models,…
A murine intestinal intraepithelial NKp46-negative innate lymphoid cell population characterized by group 1 properties
2017
The Ly49E receptor is preferentially expressed on murine innate-like lymphocytes, such as epidermal Vγ3 T cells, intestinal intraepithelial CD8αα(+) T lymphocytes, and CD49a(+) liver natural killer (NK) cells. As the latter have recently been shown to be distinct from conventional NK cells and have innate lymphoid cell type 1 (ILC1) properties, we investigated Ly49E expression on intestinal ILC populations. Here, we show that Ly49E expression is very low on known ILC populations, but it can be used to define a previously unrecognized intraepithelial innate lymphoid population. This Ly49E-positive population is negative for NKp46 and CD8αα, expresses CD49a and CD103, and requires T-bet expre…
A Library-Based Screening Strategy for the Identification of DARPins as Ligands for Receptor-Targeted AAV and Lentiviral Vectors
2021
Delivering genes selectively to the therapeutically relevant cell type is among the prime goals of vector development. Here, we present a high-throughput selection and screening process that identifies designed ankyrin repeat proteins (DARPins) optimally suited for receptor-targeted gene delivery using adeno-associated viral (AAV) and lentiviral (LV) vectors. In particular, the process includes expression, purification, and in situ biotinylation of the extracellular domains of target receptors as Fc fusion proteins in mammalian cells and the selection of high-affinity binders by ribosome display from DARPin libraries each covering more than 1012 variants. This way, DARPins specific for the …
Oxysterols: Influence on plasma membrane rafts microdomains and development of ocular diseases
2015
Oxidation of cholesterol into oxysterols is a major way of elimination of cholesterol from the liver and extrahepatic tissues, including the brain and the retina. Oxysterols are involved in various cellular processes. Numerous links have been established between oxysterols and several disorders such as neurodegenerative pathologies, retinopathies and atherosclerosis. Different components of the lipid layer such as sphingolipids, sterols and proteins participate to membrane fluidity and forme lipid rafts microdomains. Few data are available on the links between lipids rafts and oxysterols. The purpose of this review is to suggest the potential role of lipid rafts microdomains in the developm…
How alternative food networks work in a metropolitan area? An analysis of Solidarity Purchase Groups in Northern Italy
2019
AbstractOur paper focuses on Solidarity Purchase Group (SPG) participants located in a highly urbanized area, with the aim to investigate the main motivations underlining their participation in a SPG and provide a characterization of them. To this end, we carried out a survey of 795 participants involved in 125 SPGs in the metropolitan area of Milan (Italy). Taking advantage of a questionnaire with 39 questions, we run a factor analysis and a two-step cluster analysis to identify different profiles of SPG participants. Our results show that the system of values animating metropolitan SPG practitioners does not fully conform to that traditionally attributed to an alternative food network (AF…
Analysis of Spatial Disparities by a Structural Equations Model
2008
This paper presents a new analytical framework for assessing spatial disparities among countries. It takes for granted that the analysis of a country’s performance cannot be limited solely to either economic or social factors. The aim of the paper is to combine relevant economic and non-economic (mainly social) aspects of a country’s performance in an integrated logical framework. Based on this idea, a structural simultaneous equation model will be presented and estimated in order to explore the direction of the causal relationship between the economic and the non-economic aspects of a country’s performance. Furthermore, an exploration of the trajectory that each country has registered over…
Health literacy supports active aging
2020
From the individual viewpoint, active aging refers to the ability of older persons, depending on their goals, functional capacity and opportunities, to engage in desired activities. This study investigated the role of health literacy in active aging among persons differing in their number of chronic conditions. Data were collected from 948 individuals, 57% women, aged 75, 80 and 85 in 2017–2018 in the city of Jyväskylä in Central Finland. Health literacy was assessed with the 16-question version of the European Health Literacy Survey (HLS-EU-Q16), active aging with the University of Jyväskylä Active Aging Scale (UJACAS) and self-reported physician-diagnosed chronic conditions. Both health l…
In vivo consequences of cholesterol-24S-hydroxylase (CYP46A1) inhibition by voriconazole on cholesterol homeostasis and function in the rat retina
2014
International audience; Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol in neurons and participates in cholesterol homeostasis in the central nervous system, including the retina. We aimed to evaluate the consequences of CYP46A1 inhibition by voriconazole on cholesterol homeostasis and function in the retina. Rats received daily intraperitoneal injections of voriconazole (60 mg/kg), minocycline (22 mg/kg), voriconazole plus minocycline, or vehicle during five consecutive days. The rats were submitted to electroretinography to monitor retinal functionality. Cholesterol and 24S-hydroxycholesterol were measured in plasma, brain and retina by gas chromatog…
Analysis of Spatial Disparities by a Structural Equations Model
2008
This paper presents a new analytical framework for assessing spatial disparities among countries. It takes for granted that the analysis of a country’s performance cannot be limited solely to either economic or social factors. The aim of the paper is to combine relevant economic and non-economic (mainly social) aspects of a country’s performance in an integrated logical framework. Based on this idea, a structural simultaneous equation model will be presented and estimated in order to explore the direction of the causal relationship between the economic and the non-economic aspects of a country’s performance. Furthermore, an exploration of the trajectory that each country has registered over…
Cholestérol-24S-hydroxylase (CYP46A1) et homéostasie du cholestérol dans la rétine en conditions physiologiques et pathologiques
2012
Cholesterol is the major sterol found in the retina. In its free form, cholesterol is present in all cell layers of the retina, whereas cholesteryl esters mainly accumulate at the basement of the retinal pigment epithelium. The intrinsic capacity of the retina to synthetize cholesterol appears limited. Some extra-retinal pathways actively participate to cholesterol uptake to the retina. Müller glial cells may contribute to cholesterol supply to retinal neurons, especially for synaptic formation. Cholesterol accumulation or conversely deficiency have deleterious consequences on neuron survival. Maintaining the equilibrium between cholesterol supply and neosynthesis in the one hand and choles…