A fraction of plasma transthyretin (TTR) circulates in HDL through binding to apolipoprotein A-I (apoA-I). Moreover, TTR is able to cleave the C terminus of lipid-free apoA-I. In this study, we addressed the relevance of apoA-I cleavage by TTR in lipoprotein metabolism and in the formation of apoA-I amyloid fibrils. We determined that TTR may also cleave lipidated apoA-I, with cleavage being mo...

Many of the fatal neurodegenerative disorders that plague humankind, including Alzheimer's and Parkinson's disease, are connected with the misfolding of specific proteins into a surprisingly generic fibrous conformation termed amyloid. Prior to amyloid fiber assembly, many proteins populate a common oligomeric conformation, which may be severely cytotoxic. Therapeutic innovations are desperatel...

Atrial fibrillation (AF) may occur and persist due to atrial remodeling exacerbated by inflammation. However, whether inflammatory cytokines, such as serum amyloid protein A (SAA), are elevated in patients with atrial arrhythmias remains unclear. In a case-control study design, serum levels of inflammatory cytokines SAA, IL-1, IL-6, TNF-α and high...

C-reactive protein (CRP) and serum amyloid P-component (SAP) are two members of a group of plasma proteins termed pentraxins, which are composed of five identical noncovalently linked subunits that display Ca(2+)-dependent binding to a wide variety of substrates. Purified human SAP binds to CRP, only when the latter is immobilized, in a Ca(2+)-dependent manner under physiological conditions. Ex...

Proteins of the serum amyloid A (SAA) family have been remarkably conserved in evolution. Their biologic function(s) are not fully defined but they are likely to be a part of primordial host defense. We have detected a ∼ 12-kDa protein reacting with antibodies against serum amyloid A (SAA) in human colostrum by western blotting. Mass spectrometry identified the reactive species as SAA1, previou...

Background and Objective: Alzheimer’s disease (AD) is a multifactorial disease with debilitating consequences and few therapeutic strategies exist for it. With regard to antioxidant capacity and anti-β-amyloid polymerization potential of ellagic acid, this study was conducted to evaluate the effect of this substance on enhanced acetylcholinesterase reactivity in an experimental model of Alzheim...

The responses of C reactive protein, measured by radial immunodiffusion and radioimmunoassay, and serum amyloid A protein, measured by radial immunodiffusion, were compared in eight subjects with inflammation induced experimentally by intradermal injection of monosodium urate crystals. A significant increase in serum amyloid A was noted after a lag phase of eight hours, the increase in median c...

A recent study has demonstrated secondary amyloidosis in dogs treated with continuous intravenous insulin infusion. Since elevated levels of serum amyloid A protein (SAA) and diminished amyloid fibril degrading activity (AFDA) are associated with amyloidosis, we measured SAA and AFDA in ten type I diabetics treated with continuous subcutaneous insulin infusion and in five conventionally treated...

Amyloid fibrils are associated with a range of human disorders. Understanding the conversion of amyloidogenic proteins from their soluble forms to amyloid fibrils is critical for developing effective therapeutics. Previously we showed that T7 endonuclease I forms amyloid-like fibrils. Here we study the mechanism of the amyloidogenic conversion of T7 endonuclease I. We show that T7 endonuclease ...