Nontoxic Amyloid β Peptide1-42 Suppresses Acetylcholine Synthesis

Selective cytotoxicity of intracellular amyloid β peptide1–42 through p53 and Bax in cultured primary human neurons

Extracellular amyloid beta peptides (Abetas) have long been thought to be a primary cause of Alzheimer's disease (AD). Now, detection of intracellular neuronal Abeta1--42 accumulation before extracellular Abeta deposits questions the relevance of intracellular peptides in AD. In the present study, we directly address whether intracellular Abeta is toxic to human neurons. Microinjections of Abet...

Peroxynitrite mediates neurotoxicity of amyloid beta-peptide1-42- and lipopolysaccharide-activated microglia.

The amyloid beta-peptide (Abeta) activates microglia and promotes the generation of cytokines and oxygen species, including nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha), which can be either neurotoxic or neuroprotective. We show that neuron death in cocultures of rat cortical microglia and neurons activated by lipopolysaccharide (LPS) or Abeta1-42 plus interferon gamma (IFNgamm...

Globular amyloid b-peptide1)42 oligomer ) a homogenous and stable neuropathological protein in Alzheimer’s disease

Amyloid b-peptide (Ab)1)42 oligomers have recently been discussed as intermediate toxic species in Alzheimer’s disease (AD) pathology. Here we describe a new and highly stable Ab1)42 oligomer species which can easily be prepared in vitro and is present in the brains of patients with AD and Ab1)42-overproducing transgenic mice. Physicochemical characterization reveals a pure, highly water-solubl...

IL-4-Induced Selective Clearance of Oligomeric -Amyloid Peptide1–42 by Rat Primary Type 2 Microglia

Divergent synthesis of biflavonoids yields novel inhibitors of the aggregation of amyloid β (1-42).

Biflavonoids are associated with a variety of biologically useful properties. However, synthetic biflavonoids are poorly explored within drug discovery. There is considerable structural diversity possible within this compound class and large regions of potentially biologically relevant biflavonoid chemical space remain untapped or underexplored. Herein, we report the development of a modular an...