Search results for " amyloid"
showing 10 items of 130 documents
SYNTHESIS AND EVALUATION OF CURCUMIN ANALOGUES AS NEURO-PROTECTIVE AGENTS FOR THE ALZHEIMER'S DISEASE
2013
The Alzheimer's disease (AD) is the most common form of senile dementia.1 The most important role in AD is played by the aggregation process of beta-amyloid peptide (Aß), responsible for the cytotoxic effects.2 In this context, the purpose of this study was to synthesize new dicarbonyl compounds 1 structurally related to curcumin3, with anti-aggregation activity against Aß.Parallel studies involve the synthesis of heterocyclic-based curcumin-like molecules that are currently under investigation by means of in silico protocols in order to rationalize the ligand-biological target interactions.
Therapy of ATTR Cardiac Amyloidosis: Current Indications
2023
Transthyretin cardiac amyloidosis is a restrictive cardiomyopathy caused by extracellular deposition in the heart of amyloid fibrils derived from plasma transthyretin (ATTR), either in its hereditary (ATTRh) or acquired (ATTRwt) forms. Cardiac amyloidosis has a very poor prognosis if therapy is not started promptly. Therefore, it is very important to recognize cardiac amyloidosis early in order to immediately start a treatment capable of modifying the prognosis. Treatment of cardiac amyloidosis is not easy, often requiring a multidisciplinary team. New RNA-interfering drugs (such as patisiran) have been devised and are effective in the treatment of ATTRh amyloidosis. Tafamidis (a stabilizer…
Gradient-echo and CRAZED imaging for minute detection of Alzheimer plaques in an APPV717I x ADAM10-dn mouse model.
2007
Different strategies to visualize amyloid plaques with MRI at 17.6 Tesla were investigated in a novel mouse model of Alzheimer's disease (AD). Large iron-containing plaques were observed in the thalamus, but cortical plaques did not show iron deposits. Plaques in the thalamus were visualized in vivo with the use of low-resolution, 3D gradient-echo (GRE) imaging in 82 s, and with 94-microm resolution in 34 min. The feasibility of obtaining bright contrast from plaques using the COSY revamped with asymmetric z-GRE detection (CRAZED) technique was investigated in experiments on fixed brains. The original CRAZED approach provided reduced signal near the plaques (similarly to GRE imaging) and ad…
N-Terminal amino acid sequence analysis indicates that isolated atrial amyloid is derived from atrial natriuretic peptide
1988
Isolated atrial amyloid, the most frequent senile cardiac amyloid type, was chemically analysed. Amyloid fibrils obtained from a patient (NIP) were extracted and the predominant low-molecular-weight polypeptide (approximately 3.5 kDa, designated ASc2 NIP) was isolated by size exclusion high performance liquid chromatography in 60% formic acid. N-Terminal amino acid sequence analysis of this polypeptide was identical to that of the atrial natriuretic peptide alpha-hANP for the first 12 residues determined.
Concanavalin A aggregation and toxicity on cell cultures
2009
A number of neurodegenerative diseases are known to involve protein aggregation. Common mechanisms and structural properties of amyloids are thought to be involved in aggregation-related cytotoxicity. In this context we propose an experimental study on Concanavalin A (Con A) aggregation and use it as a model to study the relationship between cell toxicity and aggregation processes. Depending on solution conditions, Con A aggregation has been monitored by static and dynamic light scattering, Thioflavin T emission, and FTIR absorption. The morphology of different aggregate species was verified by means of Atomic Force Microscopy and Confocal Microscopy. During the aggregation pathway the nati…
Synthesis and evaluation of 18F-fluoroethylated benzothiazole derivatives for in vivo imaging of amyloid plaques in Alzheimer's disease
2010
Amyloid aggregates play a major role in the development of Alzheimer's disease. Targeting these aggregates by PET probes enables non-invasively the detection and quantification of amyloid deposit distribution in human brains. Based on benzothiazole core structure a series of amyloid imaging agents were developed. Currently [(11)C]2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole (Pittsburgh Compound-B (PIB) is the most specific and widely used amyloid imaging ligand. But due to the short half life of (11)C, longer lived (18)F-labeled derivatives offer logistic advantages and higher contrast images. In this work, three different [(18)F]fluoroethoxy-substituted benzothiazole derivatives ([(18…
Thioflavin T Hydroxylation at Basic pH and Its Effect on Amyloid Fibril Detection
2008
The fluorescent dye thioflavin T (ThT) is commonly used for in situ amyloid fibril detection. In this work, we focused on the spectroscopic properties and chemical stability of ThT in aqueous solution as a function of pH, temperature, and dye concentration. A reversible hydroxylation process occurs in alkaline solutions, which was characterized using a combination of UV-vis absorption spectroscopy, proton NMR, and density functional theory (DFT). On the basis of these studies, we propose a chemical structure for the hydroxylated form. Finally, by means of fluorescence spectroscopy, ThT hydroxylation effects on in situ amyloid detection have been investigated, providing new insights on the e…
Rational Management of Macroglossia Due to Acquired Systemic Amyloidosis: Does Surgery Play a Role?
2008
Haptoglobin interacts with apolipoprotein E and beta-amyloid and influences their crosstalk.
2014
Beta-amyloid accumulation in brain is a driving force for Alzheimer's disease pathogenesis. Apolipoprotein E (ApoE) represents a critical player in beta-amyloid homeostasis, but its role in disease progression is controversial. We previously reported that the acute-phase protein haptoglobin binds ApoE and impairs its function in cholesterol homeostasis. The major aims of this study were to characterize the binding of haptoglobin to beta-amyloid, and to evaluate whether haptoglobin affects ApoE binding to beta-amyloid. Haptoglobin is here reported to form a complex with beta-amyloid as shown by immunoblotting experiments with purified proteins, or by its immunoprecipitation in brain tissues …