Protein conformational diseases are associated with the aberrant accumulation of amyloid protein aggregates, but whether amyloid formation is cytotoxic or protective is unclear. To address this issue, we investigated a normally benign amyloid formed by the yeast prion [RNQ(+)]. Surprisingly, modest overexpression of Rnq1 protein was deadly, but only when preexisting Rnq1 was in the [RNQ(+)] pri...

Introduction: Alzheimer’s disease (AD) is a enfeeble neurodegenerative disorder characterized by increased β-amyloid (Aβ) deposition and neuronal dysfunction leading to impaired learning and recall. Among proposed risk factors, impaired cholinergic transmission is a main cause for incidence of disease. Methods: In the present study, effects of the intracerebroventricularly administration of an ...

Many age-related degenerative diseases, including Alzheimer's, Parkinson's, Huntington's diseases and type II diabetes, are associated with the accumulation of amyloid fibrils. The protein components of these amyloids vary widely and the mechanisms of pathogenesis remain an important subject of competing hypotheses and debate. Many different mechanisms have been postulated as significant causal...

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...

Experimental evidence suggests that the folding and aggregation of the amyloid beta-protein (Abeta) into oligomers is a key pathogenetic event in Alzheimer's disease. Inhibiting the pathologic folding and oligomerization of Abeta could be effective in the prevention and treatment of Alzheimer's disease. Here, using all-atom molecular dynamics simulations in explicit solvent, we probe the initia...

Experimental evidence suggests that the folding and aggregation of the amyloid -protein (A ) into oligomers is a key pathogenetic event in Alzheimer’s disease. Inhibiting the pathologic folding and oligomerization of A could be effective in the prevention and treatment of Alzheimer’s disease. Here, using all-atom molecular dynamics simulations in explicit solvent, we probe the initial stages of...

Neighbouring domains of multidomain proteins with homologous tandem repeats have divergent sequences, probably as a result of evolutionary pressure to avoid misfolding and aggregation, particularly at the high cellular protein concentrations. Here we combine microfluidic-mixing single-molecule kinetics, ensemble experiments and molecular simulations to investigate how misfolding between the imm...

beta-Amyloid is a 39- to 43-amino-acid neurotoxic peptide that aggregates to form the core of Alzheimer disease-associated senile (amyloid) plaques. No satisfactory hypothesis has yet been proposed to explain the mechanism of beta-amyloid aggregation and toxicity. We present mass spectrometric and electron paramagnetic resonance spin trapping evidence that beta-amyloid, in aqueous solution, fra...

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...