Five similar anthocyanidin molecules display distinct disruptive effects and mechanisms of action on Aβ protofibril: A molecular dynamic simulation study.

Alzheimer's disease (AD) is associated with the deposition of amyloid-β (Aβ) fibrillary aggregates. Disaggregation of Aβ fibrils is considered as one of the promising AD treatments. Recent experimental studies showed that anthocyanidins, one type of flavonoids abundant in fruits/vegetables, can disaggregate Aβ fibrillary aggregates.

Dissecting the Inhibitory Mechanism of the αB-Crystallin Domain against Aβ Aggregation and Its Effect on Aβ Protofibrils: A Molecular Dynamics Simulation Study.

Alzheimer's disease (AD) is related to the misfolding and aggregation of amyloid-β (Aβ) protein, and its major pathological hallmark is fibrillary β-amyloid plaques. Impeding the formation of Aβ β-structure-rich aggregates and dissociating Aβ fibrils are considered potent strategies to suppress the onset and progression of AD. As a molecular chaperone, human αB-crystallin has received extensive attention in the inhibition of protein aggregation.

Molecular mechanisms of resveratrol and EGCG in the inhibition of Aβ aggregation and disruption of Aβ protofibril: similarities and differences.

The aggregation of amyloid-β protein (Aβ) into fibrillary deposits is implicated in Alzheimer's disease (AD), and inhibiting Aβ aggregation and clearing Aβ fibrils are considered as promising strategies to treat AD. It has been reported that resveratrol (RSV) and epigallocatechin-3-gallate (EGCG), two of the most extensively studied natural polyphenols, are able to inhibit Aβ fibrillization and remodel the preformed fibrillary aggregates into amorphous, non-toxic species. However, the mechanisms by which RSV inhibits Aβ aggregation and disrupts Aβ protofibril, as well as the inhibitory/disruptive mechanistic similarities and differences between RSV and EGCG, remain mostly elusive.

A Comprehensive Insight into the Mechanisms of Dopamine in Disrupting Aβ Protofibrils and Inhibiting Aβ Aggregation.

Fibrillary aggregates of amyloid-β (Aβ) are the pathological hallmark of Alzheimer's disease (AD). Clearing Aβ deposition or inhibiting Aβ aggregation is a promising approach to treat AD. Experimental studies reported that dopamine (DA), an important neurotransmitter, can inhibit Aβ aggregation and disrupt Aβ fibrils in a dose-dependent manner.

Natural stereoisomeric flavonoids exhibit different disruptive effects and the mechanism of action on Aβ protofibril.

Our simulations reveal that two enantiomeric catechins display a better disruptive effect on Aβ42 protofibril than their stereoisomer epicatechin. Unexpectedly, we find that catechins adopt both collapsed and extended states, while epicatechin populates only an extended state. Their different protofibril-disruptive effects are mostly attributed to the steric effect caused by the conformational differences.

Serotonin and Melatonin Show Different Modes of Action on Aβ Protofibril Destabilization.

Alzheimer's disease (AD) is associated with the aberrant self-assembly of amyloid-β (Aβ) protein into fibrillar deposits. The disaggregation of Aβ fibril is believed as one of the major therapeutic strategies for treating AD. Previous experimental studies reported that serotonin (Ser), one of the indoleamine neurotransmitters, and its derivative melatonin (Mel) are able to disassemble preformed Aβ fibrils.

Green tea extract EGCG plays a dual role in Aβ protofibril disruption and membrane protection: A molecular dynamic study.

Amyloid plaques accumulated by the amyloid-β (Aβ) fibrillar aggregates are the major pathological hallmark of the Alzheimer's disease (AD). Inhibiting aggregation and disassembling preformed fibrils of Aβ by natural small molecules have developed into a promising therapeutic strategy for AD. Previous experiments reported that the green tea extract epigallocatechin-3-gallate (EGCG) can disrupt Aβ fibril and reduce Aβ cytotoxicity.

Green Tea Extracts EGCG and EGC Display Distinct Mechanisms in Disrupting Aβ Protofibril.

The amyloid beta (Aβ) fibrillar aggregate is the hallmark of Alzheimer's disease (AD). Disassembling preformed fibril or inhibiting Aβ aggregation is considered as a therapeutic strategy for AD. Increasing evidence shows that green tea extracts, epigallocatechin-3-gallate (EGCG, containing an extra gallic acid ester group compared to EGC) and epigallocatechin (EGC), can disassociate Aβ fibrils and attenuate Aβ toxicity.

Structural Polymorphism in a Self-Assembled Tri-Aromatic Peptide System.

Self-assembly is a process of key importance in natural systems and in nanotechnology. Peptides are attractive building blocks due to their relative facile synthesis, biocompatibility, and other unique properties. Diphenylalanine (FF) and its derivatives are known to form nanostructures of various architectures and interesting and varied characteristics.

Conformational dynamics of cancer-associated MyD88-TIR domain mutant L252P (L265P) allosterically tilts the landscape toward homo-dimerization.

MyD88 is an essential adaptor protein, which mediates the signaling of the toll-like and interleukin-1 receptors' superfamily. The MyD88 L252P (L265P) mutation has been identified in diffuse large B-cell lymphoma. The identification of this mutation has been a major advance in the diagnosis of patients with aldenstrom macroglobulinemia and related lymphoid neoplasms.

Insights Into the Allosteric Inhibition of the SUMO E2 Enzyme Ubc9.

Conjugation of the small ubiquitin-like modifier (SUMO) to protein substrates is an important disease-associated posttranslational modification, although few inhibitors of this process are known. Herein, we report the discovery of an allosteric small-molecule binding site on Ubc9, the sole SUMO E2 enzyme. An X-ray crystallographic screen was used to identify two distinct small-molecule fragments that bind to Ubc9 at a site distal to its catalytic cysteine.