Phosphorylation remodels amyloid

Brazilin inhibits amyloid β-protein fibrillogenesis, remodels amyloid fibrils and reduces amyloid cytotoxicity

Soluble amyloid β-protein (Aβ) oligomers, the main neurotoxic species, are predominantly formed from monomers through a fibril-catalyzed secondary nucleation. Herein, we virtually screened an in-house library of natural compounds and discovered brazilin as a dual functional compound in both Aβ42 fibrillogenesis inhibition and mature fibril remodeling, leading to significant reduction in Aβ42 cy...

Nuclear CaMKII enhances histone H3 phosphorylation and remodels chromatin during cardiac hypertrophy

Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in pathological cardiac hypertrophy, but the mechanisms by which it modulates gene activity in the nucleus to mediate hypertrophic signaling remain unclear. Here, we report that nuclear CaMKII activates cardiac transcription by directly binding to chromatin and regulating the phosphorylation of histone H3 at serine-10....

Notch remodels junctions

Nicotinic Acetylcholine Receptors Mediate -Amyloid Peptide-induced Tau Protein Phosphorylation*

The Alzheimer’s disease pathogenic peptide, -amyloid42 (A 42), induces tau protein phosphorylation. Because hyperphosphorylated tau is a consistent component of neurofibrillary tangles, a pathological hallmark of Alzheimer’s disease, we investigated the signaling molecules involved in A 42-induced tau phosphorylation. We show that A 42 elicited rapid and reversible tau protein phosphorylation o...

Phosphorylation modifies the molecular stability of β-amyloid deposits

Protein aggregation plays a crucial role in neurodegenerative diseases. A key feature of protein aggregates is their ubiquitous modification by phosphorylation. Little is known, however, about the molecular consequences of phosphorylation of protein aggregates. Here we show that phosphorylation of β-amyloid at serine 8 increases the stability of its pathogenic aggregates against high-pressure a...