Search results for "Amy"

Amyloid Fibrils Formation of Concanavalin A at Basic pH

2011

Mechanisms of partial unfolding and aggregation of proteins are of extreme interest in view of the fact that several human pathologies are characterized by the formation and deposition of protein-insoluble material, mainly composed of amyloid fibrils. Here we report on an experimental study on the heat-induced aggregation mechanisms, at basic pH, of concanavalin A (ConA), used as a model system. Thioflavin T (ThT) fluorescence and multiangle light scattering allowed us to detect different intertwined steps in the formation of ConA aggregates. In particular, the ThT fluorescence increase, observed in the first phase of aggregation, reveals the formation of intermolecular β-sheet structure wh…

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…

Familial Amyloid Polyneuropathy

2013

Familial amyloid polyneuropathy (FAP; also known as familiar amyloidosis and hereditary amyloidosis) is an autosomal dominant inherited disease due to mutations of the transthyretin (TTR) gene coding for the corresponding protein, consisting of 127 amino acids. The gene is located on chromosome 18q. More than 100 different mutations are known. Other mutant precursor proteins produced in the liver, such as apolipoprotein I and II, lysozyme and fibrinogen Aα, may be of etiological importance as well. Amyloidogenic mutations of the TTR gene lead to decreased stability of the corresponding protein and subsequently to extracellular deposition of amyloid in several tissues (peripheral and autonom…

Amyloid-Like Superstructures: mechanisms of formation and morphologies

2014

Emerging contributions of formyl peptide receptors to neurodegenerative diseases.

2021

Abstract Inflammation is a central element of many neurodegenerative diseases. Formyl peptide receptors (FPRs) can trigger several receptor-dependent signal transduction pathways that play a key role in neuroinflammation and neurodegeneration. They are chemotactic receptors that help to regulate pro- and anti-inflammatory responses in most mammals. FPRs are primarily expressed in the immune and nervous systems where they interact with a complex pattern of pathogen-derived and host-endogenous molecules. Mounting evidence points towards a contribution of FPRs – via neuropathological ligands such as Amyloid beta, and neuroprotective ligands such as Humanin, Lipoxin A4, and Annexin A1 – to mult…

Genistein effect on cognition in prodromal Alzheimer's disease patients : the GENIAL clinical trial

2022

Background: Delaying the transition from minimal cognitive impairment to Alzheimer’s dementia is a major concern in Alzheimer’s disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet efective substances are recommended. There is a need to develop new drugs to delay Alzheimer’s dementia. We have taken a nutritional supplement approach with genistein, a chemically defned polyphenol that acts by multimodal specifc mechanisms. Our group previously showed that genistein supplementation is efective to treat the double transgenic (APP/PS1) AD animal model. Methods: In this…

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…

Nonsteroidal Anti-inflammatory Drugs (NSAIDs) and Derived Aβ42-Lowering Molecules for Treatment and Prevention of Alzheimer's Disease (AD)

2007

Concanavalin A fibrils formation from Coagulation of Long-lived" Crinkled" Intermediates

2013

Cellular Prion Protein Participates in Amyloid-β Transcytosis across the Blood—Brain Barrier

2012

The blood—brain barrier (BBB) facilitates amyloid-β (Aβ) exchange between the blood and the brain. Here, we found that the cellular prion protein (PrPc), a putative receptor implicated in mediating Aβ neurotoxicity in Alzheimer's disease (AD), participates in Aβ transcytosis across the BBB. Using an in vitro BBB model, [125I]-Aβ1–40 transcytosis was reduced by genetic knockout of PrPc or after addition of a competing PrPc-specific antibody. Furthermore, we provide evidence that PrPc is expressed in endothelial cells and, that monomeric Aβ1–40 binds to PrPc. These observations provide new mechanistic insights into the role of PrPc in AD.