Some of Leeds’ top biological researchers have received two new Wellcome Discovery Awards, confirming the university’s status as a centre of excellence in biological research.

Nature Communications - This study demonstrates how to combine molecular dynamics computer simulations with experimental biophysical data to determine accurate atomic-resolution ensembles of...

The obsession with economic output as a measure of human development puts sustainability on the back burner. Researchers can now help to devise better indicators.

Preliminary results from a small trial offer the clearest evidence yet that the brain disease’s progression can be slowed.

Alpha-synuclein (αS) is an intrinsically disordered protein (IDP) that can self-assemble into amyloid fibrils, undergoing a transition from disordered monomers to ordered β-sheet-rich fibrils. The amy...

Alzheimer's disease and prion diseases are linked to unnatural aggregation of proteins into amyloid fibrils.

The interplay between tau and amyloid-β (Aβ) in the development of Alzheimer’s disease is not fully understood. It has now been shown that tau’s microtubule-binding repeat regions, which contain a com...

The development of a universal protein coarse-grained model has been a long-standing challenge. A coarse-grained model with chemical transferability has now been developed by combining deep-learning m...

Predicting small-molecule partitioning into biomolecular condensates is the key to developing drugs that selectively target aberrant condensates. However, the molecular mechanisms underlying small-mol...

A method for de novo design of peptide macrocyles called RFpeptides has been developed. RFpeptides is an extension of RoseTTAFold2 and RFdiffusion and combines structure prediction and protein backbon...

Proteins are among the most studied molecules in biology, yet new research from the University of Göttingen shows they can still hold surprising secrets. Researchers have discovered previously undetected ...

Over time biomolecular condensates' redox activity drops and tangled aggregates linked to conditions like Alzheimer's build-up

Nature - Scientists also identified anti-ageing drugs and experimental compounds that could target the genes to reverse decline.

Spatial transcriptomics reveals distinct microglial mechanisms driving amyloid-β clearance in both passively and actively immunized patients with Alzheimer’s disease.

Nature - An amyloid protein targeted by Alzheimer’s disease therapies seems to be involved in normal mental decline.

Amyloid formation is involved in widespread health conditions such as Alzheimer’s disease, Parkinson’s disease, and type-2 diabetes. Amyloid fibrils have a similar cross-β architecture, but fibrils formed by a single protein sequence can have diverse structures, varying with time, self-assembly conditions, and sequence modifications. Fibril structure has been proposed to be diagnostic of disease, but why different structures result under different conditions, especially in vitro, remains elusive. We previously identified a small molecule, YX-I-1, which inhibits in vitro amyloid formation by islet amyloid polypeptide (IAPP), a peptide hormone whose amyloid formation is involved in type-2 diabetes. Here, using YX-I-1 as a lead, we identified regulator-approved drugs with similar structures by chemical similarity analysis and substructure searches and monitored the effect of 24 of these potential ligands on IAPP amyloid assembly in vitro. We show that one such compound, canagliflozin (Invokana), a type-2 diabetes drug already in clinical use, can strongly delay the kinetics of IAPP amyloid formation, an activity independent of its intended mode of action [sodium-glucose linked transporter 2 (SGLT2) inhibitor] that may have important therapeutic implications. Combining analysis of amyloid self-assembly kinetics, biophysical characterization of monomer and fibril binding, and cryo-EM of the assembly products, we show that YX-I-1 and canagliflozin target IAPP early in aggregation, remodeling the energy landscape of primary nucleation and profoundly altering the resulting fibril structures. Early binding events thus imprint long-lasting effects on the amyloid structures that form.

Slippery proteins in the brain’s blood vessels form a protective barrier that breaks down with age, studies in mice show.