Cholesterol is an integral component of neuronal membranes and recent evidence has shown that it regulates amyloid-beta protein precursor processing to form amyloid-beta peptides, which are a major constituent of cerebral amyloid plaques associated with Alzheimer's disease. 27-Hydroxycholesterol (27OHC) is synthesized from cholesterol via sterol 27-hydroxylase (CYP27A1) in the brain and, unlike...

Type 2 diabetes is characterized by a progressive loss of beta-cell function throughout the course of the disease. The pattern of loss is an initial defect in early or first-phase insulin secretion, followed by a decreasing maximal capacity of glucose to potentiate all nonglucose signals. Last, a defective steady-state and basal insulin secretion develops, leading to complete beta-cell failure ...

Self-assembly of amyloid beta into fibrillar plaques is characteristic of Alzheimer's disease and oligomers of this peptide are believed to be involved in neurodegeneration. Natural organic dyes, such as congo red and curcumin, bind tightly to amyloid beta and, at higher concentrations, block its self-assembly. The ability of these molecules to prevent amyloid accumulation has generated interes...

Oxidative stress is one of the pathological mechanisms responsible for the beta- amyloid cascade associated with Alzheimer's disease (AD). Previous studies have demonstrated the role of carnosic acid (CA), an effective antioxidant, in combating oxidative stress. A progressive cognitive decline is one of the hallmarks of AD. Thus, we attempted to determine whether the administration of CA protec...

Genetic evidence suggests a role for apolipoprotein E (apoE) in Alzheimer's disease (AD) amyloidogenesis. Here, amyloid-associated apoE from 32 AD patients was purified and characterized. We found that brain amyloid-associated apoE apparently exists not as free molecules but as complexes with polymers of the amyloid beta peptide (A beta). Brain A beta-apoE complexes were detected irrespective o...

Amyloid-beta peptide, which accumulates in senile plaques in Alzheimer's disease, is derived from the amyloid precursor protein (APP) by proteolytic processing. beta-secretase (Asp2), which cleaves APP at the N-terminus of amyloid-beta, has recently been identified to be the protease BACE. In the present study, we examined the subcellular localization of interactions between APP and BACE by usi...

Neprilysin is a transmembrane zinc metallopeptidase that degrades a wide range of peptide substrates. It has received attention as a potential therapy for Alzheimer's disease due to its ability to degrade the peptide amyloid beta. However, its broad range of peptide substrates has the potential to limit its therapeutic use due to degradation of additional peptides substrates that tightly regula...

Amyloids and prion proteins are clinically and biologically important beta-structures, whose supersecondary structures are difficult to determine by standard experimental or computational means. In addition, significant conformational heterogeneity is known or suspected to exist in many amyloid fibrils. Recent work has indicated the utility of pairwise probabilistic statistics in beta-structure...

In the brains of aged humans and cases of Alzheimer disease, deposits of amyloid in senile plaques are located in proximity to nerve processes. The principal component of this extracellular amyloid is beta/A4, a peptide derived from a larger amyloid precursor protein (APP), which is actively expressed in brain and systemic organs. Mechanisms that result in the proteolysis of APP to form beta/A4...

A new study in fruit flies suggests modulation of neural activity links sleep and Alzheimer's disease. Both sleep loss and amyloid beta increase neural excitability, which reinforces the accumulation of amyloid beta and shortens lifespan.