Metabolites from Marine Macroorganisms of the Red Sea Acting as Promoters or Inhibitors of Amylin Aggregation.

Amylin is part of the endocrine pancreatic system that contributes to glycemic control, regulating blood glucose levels. However, human amylin has a high tendency to aggregate, forming isolated amylin deposits that are observed in patients with type 2 diabetes mellitus. In search of new inhibitors of amylin aggregation, we undertook the chemical analyses of five marine macroorganisms encountered in high populations in the Red Sea and selected a panel of 10 metabolites belonging to different chemical classes to evaluate their ability to inhibit the formation of amyloid deposits in the human amylin peptide.

Exploring the central region of amylin and its analogs aggregation: the influence of metal ions and residue substitutions.

Human amylin (hIAPP) is found in the form of amyloid deposits within the pancreatic cells of nearly all patients diagnosed with type 2 diabetes mellitus (T2DM). However, rat amylin (rIAPP) and pramlintide - hIAPP analogs - are both non-toxic and non-amyloidogenic. Their primary sequences exhibit only slight variations in a few amino acid residues, primarily concentrated in the central region, spanning residues 20 to 29.

Mitigating diabetes associated with reactive oxygen species (ROS) and protein aggregation through pharmacological interventions.

Diabetes mellitus, a complex metabolic disorder, presents a growing global health challenge. In 2021, there were 529 million diabetics worldwide. At the super-regional level, Oceania, the Middle East, and North Africa had the highest age-standardized rates.

Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases.

Neurodegenerative diseases are a serious and widespread global public health burden amongst aging populations. The total estimated worldwide global cost of dementia was US$818 billion in 2015 and has been projected to rise to 2 trillion US$ by 2030. While advances have been made to understand different neurodegenerative disease mechanisms, effective therapeutic strategies do not generally exist.

Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin.

Metformin has been used for decades in millions of type 2 diabetes mellitus patients. In this time, correlations between metformin use and the occurrence of other disorders have been noted, as well as unpredictable metformin side effects. Diabetes is a significant cancer risk factor, but unexpectedly, metformin-treated diabetic patients have lower cancer incidence.

Undercover Toxic Ménage à Trois of Amylin, Copper (II) and Metformin in Human Embryonic Kidney Cells.

In recent decades, type 2 diabetes complications have been correlated with amylin aggregation, copper homeostasis and metformin side effects. However, each factor was analyzed separately, and only in some rare cases copper/amylin or copper/metformin complexes were considered. We demonstrate for the first time that binary metformin/amylin and tertiary copper (II)/amylin/metformin complexes of high cellular toxicity are formed and lead to the formation of aggregated multi-level lamellar structures on the cell membrane.

Living with the enemy: from protein-misfolding pathologies we know, to those we want to know.

Conformational diseases are caused by the aggregation of misfolded proteins. The risk for such pathologies develops years before clinical symptoms appear, and is higher in people with alpha-1 antitrypsin (AAT) polymorphisms. Thousands of people with alpha-1 antitrypsin deficiency (AATD) are underdiagnosed.

"What Doesn't Kill You Makes You Stronger": Future Applications of Amyloid Aggregates in Biomedicine.

Amyloid proteins are linked to the pathogenesis of several diseases including Alzheimer's disease, but at the same time a range of functional amyloids are physiologically important in humans. Although the disease pathogenies have been associated with protein aggregation, the mechanisms and factors that lead to protein aggregation are not completely understood. Paradoxically, unique characteristics of amyloids provide new opportunities for engineering innovative materials with biomedical applications.

Using NMR spectroscopy to investigate the role played by copper in prion diseases.

Prion diseases are a group of rare neurodegenerative disorders that develop as a result of the conformational conversion of normal prion protein (PrP) to the disease-associated isoform (PrP). The mechanism that actually causes disease remains unclear. However, the mechanism underlying the conformational transformation of prion protein is partially understood-in particular, there is strong evidence that copper ions play a significant functional role in prion proteins and in their conformational conversion.

Copper(II) and Amylin Analogues: A Complicated Relationship.

Protein aggregation has attracted substantial interest because of its role in causing many serious illnesses, such as neurodegenerative diseases and type II diabetes. Recent studies have shown that protein aggregation can be prevented by forming metal ion complexes with a target protein, which affects their conformation in solution and their physical properties, such as aggregation. Thus, understanding the interactions between aggregating molecules and bioactive metal ions such as Cu is beneficial for new drug discovery.

Interaction of amylin species with transition metals and membranes.

Islet Amyloid Polypeptide (IAPP), also known as amylin, is a 37-amino-acid peptide hormone that is secreted by pancreatic islet β-cells. Amylin is complementary to insulin in regulating and maintaining blood glucose levels in the human body. The misfolding and aggregation of amylin is primarily associated with type 2 diabetes mellitus, which is classified as an amyloid disease.