Corneal stromal dystrophies are a group of genetic disorders that may be caused by mutations in the transforming growth factor β-induced (TGFBI) gene which results in the aggregation and deposition of mutant proteins in various layers of the cornea. The type of amino acid substitution dictates the age of onset, anatomical location of the deposits, morphological features of deposits (amyloid, am...

The BRICHOS domain is associated with proliferative, degenerative and amyloid diseases, and it has been shown to inhibit fibril formation and toxicity of the Alzheimer's disease-associated amyloid β-peptide. ProSP-C (prosurfactant protein C) BRICHOS binds to stretches of hydrophobic amino acid residues, which are unfolded or in β-strand conformation, suggesting that it may have broad anti-amylo...

Background: Inhibition of pathogenic protein aggregation by small molecules is poorly understood. Results: Aggregation inhibitors alter the free energy landscape of a relevant fragment of Alzheimer's amyloid-β protein in subtle but complex fashion. Conclusion: Intrinsic disorder of disease proteins persists at the level of binding small molecules. Significance: Hallmark characteristics and effi...

Cx3cr1, the receptor for the chemokine Cx3cl1 (fractalkine), has been implicated in the progression and severity of Alzheimer's disease-like pathology in mice, but the underlying mechanisms remain unclear. A complicating factor is that Cx3cr1 has been demonstrated in both neurons and microglia. Here, we have dissected the differences between neuronal and microglial Cx3cr1, specifically by compa...

Alzheimer's disease is a rising threat for modern societies as more and more people reach old age. To date, there is no effective treatment for this condition. In this study, we investigated the potential of Glycyrrhiza uralensis to counteract amyloid-β toxicity, one of the key features of Alzheimer's disease. An LC-MS/MS analysis revealed glycyrrhizic acid and glycosylated forms of isoliquirit...

Considerable mechanistic insight has been gained into amyloid aggregation; however, a large number of non-amyloid protein aggregates are considered "amorphous," and in most cases, little is known about their mechanisms. Amorphous aggregation of γ-crystallins in the eye lens causes cataract, a widespread disease of aging. We combined simulations and experiments to study the mechanism of aggregat...

How, and why, different proteins form amyloid fibrils is most often studied in vitro using a single purified protein sequence. However, many amyloid diseases involve co-aggregation of different protein species, including proteins with/without post-translational modifications (e.g., different strains of PrP), proteins of different length (e.g., β₂-microglobulin and ΔN6, Aβ40, and Aβ42), sequence...

Aggregation T aggregation of proteins and polypeptides is a major problem in the laboratory and in biotechnology, and is a serious issue in biology and human health. Protein aggregation is a topic that is ripe for investigation by physical chemical and biophysical methods, as well as by molecular dynamics (MD) simulations, and by more coarse grained modeling and analytical theory. Much recent a...

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, responsible for nearly two-thirds of all dementia cases. In this review, we report potential AD treatment strategies focusing on natural polyphenol molecules (green chemistry) and more specifically inhibition polyphenol-induced amyloid aggregation/disaggregation pathways: in bulk biosurfaces. We discuss how thes...

Recent experimental studies have shown that amyloid fibril formed by aggregation of β peptide exhibits excellent mechanical properties comparable to other protein materials such as actin filaments and microtubules. These excellent mechanical properties of amyloid fibrils are related to their functional role in disease expression. This indicates the necessity to understand how an amyloid fibril ...