Search results for "Alzheimer Disease"
showing 10 items of 428 documents
Retinoic Acid and the Gut Microbiota in Alzheimer’s Disease: Fighting Back-to-Back?
2019
Background:There is growing evidence that the gut microbiota may play an important role in neurodegenerative diseases such as Alzheimer’s disease. However, how these commensals influence disease risk and progression still has to be deciphered.Objective:The objective of this review was to summarize current knowledge on the interplay between gut microbiota and retinoic acid. The latter one represents one of the important micronutrients, which have been correlated to Alzheimer’s disease and are used in initial therapeutic intervention studies.Methods:A selective overview of the literature is given with the focus on the function of retinoic acid in the healthy and diseased brain, its metabolism…
Potential Roles of Peroxisomes in Alzheimer's Disease and in Dementia of the Alzheimer's Type
2012
In Alzheimer's disease (AD) and dementia of the Alzheimer's type (DAT), the role played by peroxisomes is not well known. Peroxisomes are present in all eukaryotic cells, with the exception of erythrocytes. They are involved in the β-oxidation process of long-chain fatty acids, very-long-chain fatty acids, and branched-chain fatty acids. They participate in the α-oxidation of phytanic acid, the biosynthesis of bile acids, and the breakdown of eicosanoids. Peroxisomes are also involved in the synthesis of specific fatty acids such as docosahexaenoic acid (DHA), which is essential for the brain and retina, and plasmalogens (PLGN), which play crucial roles in neural cells and are essential com…
A practical entry to β-aryl-β-alkyl amino alcohols: application to the synthesis of a potent BACE1 inhibitor
2012
The 1,2-addition of alkyl Grignard reagents to readily available N-tert-butanesulfinyl ketimines, bearing an α-silyloxy substituent, proceeds in high yields and excellent diastereocontrol. The utility of the present method was demonstrated by the synthesis, in enantiomerically pure form, of one recently disclosed β-secretase (BACE1) inhibitor.
(±)- BIGI-3h: Pentatarget-Directed Ligand combining Cholinesterase, Monoamine Oxidase, and Glycogen Synthase Kinase 3β Inhibition with Calcium Channe…
2021
Multitarget-directed ligands (MTDLs) are considered a promising therapeutic strategy to address the multifactorial nature of Alzheimer's disease (AD). Novel MTDLs have been designed as inhibitors of human acetylcholinesterases/butyrylcholinesterases, monoamine oxidase A/B, and glycogen synthase kinase 3β and as calcium channel antagonists via the Biginelli multicomponent reaction. Among these MTDLs, (±)-BIGI-3h was identified as a promising new hit compound showing in vitro balanced activities toward the aforementioned recognized AD targets. Additional in vitro studies demonstrated antioxidant effects and brain penetration, along with the ability to inhibit the aggregation of both τ protein…
Receptor for advanced glycation end products is subjected to protein ectodomain shedding by metalloproteinases.
2008
The receptor for advanced glycation end products (RAGE) is a 55-kDa type I membrane glycoprotein of the immunoglobulin superfamily. Ligand-induced up-regulation of RAGE is involved in various pathophysiological processes, including late diabetic complications and Alzheimer disease. Application of recombinant soluble RAGE has been shown to block RAGE-mediated pathophysiological conditions. After expression of full-length RAGE in HEK cells we identified a 48-kDa soluble RAGE form (sRAGE) in the culture medium. This variant of RAGE is smaller than a 51-kDa soluble version derived from alternative splicing. The release of sRAGE can be induced by the phorbol ester PMA and the calcium ionophore c…
Classification of healthy, Alzheimer and Parkinson populations with a multi-branch neural network
2022
Signal processing, for delimitation of the target events and parametrization, is usually required when instrumented assessment is conducted to determine an individual’s functional status. However, these procedures may rule out relevant information obtained by sensors. To prevent this, the use of models based on neural networks that automatically extract relevant features from the raw signal may improve the characterization of the functional status. Thus, the aim of the study was to determine the classification accuracy of a multi-head convolutional layered neural network (CNN) using a simple functional mobility test in people with different conditions. The raw data from an inertial sensor e…
Biodistribution of Insulin-Nanogels in Mouse: A Preliminary Study for the Treatment of Alzheimer's Disease
2017
A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer's disease (AD) neurodegeneration. Thus, administration of insulin could be a strategy for AD treatment. For this aim we have designed, synthesized and characterized a nanogel system (NG) that has been conjugated to insulin molecules (NG-In) to deliver the protein into the brain, as a tool for the development of a new therapy against AD. In our preclinical study in mice, intraperitoneal injection of fluorescent-labeled NG has allowed to determine the biodistribution of NG vs time in the whole body and its clearance th…
Ajokyvyn arviointi MoCA-menetelmällä Alzheimerin taudin varhaisvaiheessa
2019
Vertaisarvioitu Lähtökohdat Tutkimme Montreal Cognitive Assessment (MoCA) -menetelmän soveltuvuutta varhaista Alzheimerin tautia sairastavien potilaiden ajokyvyn arviointiin. Selvitimme myös menetelmän herkkyyttä tunnistaa kognitiomuutoksia. Menetelmät Tutkimus sisälsi haastattelun, kognitiivisen arvioinnin (MoCA), ajon simulaattorilla ja oman ajamisen arvioinnin. Siihen osallistui 7 potilasta ja 17 tervettä ikätoveria. Tulokset Potilaat suoriutuivat verrokkeja heikommin MoCA-testissä ja simulaattoriajossa. Arvio omasta suoriutumisesta ajossa oli heillä merkitsevästi parempi kuin verrokeilla. Potilaat saivat testipisteitä keskimäärin 18,6 ja verrokit 27,4. Simulaattoriajossa potilaat tekivä…
Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM 10
2001
Biochemical, epidemiological, and genetic findings demonstrate a link between cholesterol levels, processing of the amyloid precursor protein (APP), and Alzheimer's disease. In the present report, we identify the α-secretase ADAM 10 ( a d isintegrin a nd m etalloprotease) as a major target of the cholesterol effects on APP metabolism. Treatment of various peripheral and neural cell lines with either the cholesterol-extracting agent methyl-β-cyclodextrin or the hydroxymethyl glutaryl-CoA reductase inhibitor lovastatin resulted in a drastic increase of secreted α-secretase cleaved soluble APP. This strong stimulatory effect was in the range obtained with phorbol esters and was further increa…
Potential drug-drug interaction between duloxetine and acenocoumarol in a patient with Alzheimer's disease
2007
Abstract Background : Recent evidence suggests that duloxetine may increase the effect of warfarin, thereby increasing the possibility of bleeding. However, a MEDLINE search for articles published between 1980 and May 2007 (terms: duloxetine , anticoagulants , acenocoumarol , and interaction ; no language restriction) did not yield any reports of an interaction between concomitant use of duloxetine and acenocoumarol. Objective : The aim of this study was to describe a potential drug-drug interaction between duloxetine and acenocoumarol in a patient with Alzheimer's disease. The possible mechanism of this potential interaction is examined. Case summary : This report presents the case of a 63…