Narrow Results

SINGAPORE – A New Way of Looking at Cancer

SINGAPORE – Novel Discovery by NUS Scientists Improves Profiling of AML Patients for Targeted Therapies

SINGAPORE – Red Meat Consumption Linked with Increased Risk of Developing Kidney Failure

SINGAPORE – Thomson Medical and UK-based Cell Therapy Limited Collaborate on Stem Cell Research to Develop Regenerative Medicines

UNITED STATES – New Biomaterial Developed for Injectable Neuronal Control

UNITED STATES – Research Shines Light on Lesser Known Form of Vitamin D in Foods

UNITED STATES – MRIGlobal to Lead International Research Collaboration for Tularemia Vaccine

INDIA – Improving Agricultural Yield and Quality through Tissue Culture Technology

TAIWAN – A Cascade of Protein Aggregation Bombards Mitochondria for Neurodegeneration and Apoptosis under WWOX Deficiency

SINGAPORE – Letting Go.

SINGAPORE & JAPAN – ASLAN Pharmaceuticals Announces First Patient Enrolled in Phase 1 Study of Varlitinib in Japan.

JAPAN & UNITED STATES – Santen and twoXAR Announce Strategic Research Collaboration to Discover New Glaucoma Treatments.

UNITED STATES – New Study Finds Extensive Use of Fluorinated Chemicals in Fast Food Wrappers.

UNITED STATES – What Doesn’t Kill You Makes You Stronger.

UNITED STATES – Non-Invasive Test Offers Quick Skin Cancer Diagnosis.

UNITED STATES – Life Under Pressure.

AUSTRALIA & THAILAND – Commencement of BIT225 Phase 2 HIV-1 Clinical Trial.

CANADA – Understanding the Genetics of Human Height.

TAIWAN – TLC Announces Collaboration with CMUH in Exploring Solutions for Unmet Medical Needs in Oncology and Osteoarthritis.

Enzymatic reactions occurring in vivo on lipid membranes can be influenced by various factors including macromolecular crowding in general and substrate aggregation in particular. In academic studies, the role of these factors can experimentally be clarified by tracking single-enzyme kinetics occurring on individual lipid vesicles. To extend the conceptual basis for such experiments, we analyze herein the corresponding kinetics mathematically with emphasis on the role of substrate aggregation. In general, the aggregation may occur on different length scales. Small aggregates may e.g. contain a few proteins or peptides while large aggregates may be mesoscopic as in the case of lipid domains which can be formed in the membranes composed of different lipids. We present a kinetic model describing comprehensively the effect of aggregation of the former type on the dependence of the reaction rate on substrate membrane concentration. The results obtained with physically reasonable parameters indicate that the aggregation-related deviations from the conventional Michaelis–Menten kinetics may be appreciable.

Special Issue Comments: This theoretical article is focused on single-enzyme reactions occurring in parallel with substrate aggregation on individual vesicles. This subject is related to a few Special Issue articles concerning enzyme dynamics^6,7 and function⁸ and mathematical aspects of stochastic kinetics.⁹

Amyloids are highly ordered aggregates of misfolded proteins, related to a large number of neurodegenerative diseases including Alzheimer’s, Parkinson’s, type II diabetes and many other debilitating disorders. The misfolded proteins are most commonly $\beta$-sheet rich fibrillar aggregates, and one of the most common therapeutic approaches for the treatment of these disorders is inhibiting the formation of fibrillar aggregates. To date, a myriad of compounds have been introduced for this purpose, however poor water solubility and low bioavailability are major restrictions to achieve this purpose. To overcome these limitations, polymeric materials could be a great choice because of their many unique properties. Furthermore, oxidative stress is a key factor associated with the aforementioned disorders. In this context, natural polyphenolic compounds are attracting attention due to their abundance, potential antioxidant activities and nontoxic nature. Considering the importance of antioxidant agents in preventing the protein aggregation process, the design of novel antioxidant polymers has become a challenging task nowadays. Based on these perspectives, this review aims to provide an overall idea about the protein misfolding process, mechanistic pathway, and therapeutic approaches. The main focus of this review is the use of antioxidant molecules and the integration of natural polyphenol-based antioxidants with polymers for designing next-generation potential anti-amyloidogenic agents.

A substantial portion of the cellular homeostasis network is dedicated to managing the consequences of protein aggregation, a process that cannot be avoided. In recent decades, research into human diseases, including neurodegenerative disorders, diabetes, and various forms of amyloidosis, has highlighted the profound impact of protein aggregation and its variants on human health. While numerous experimental techniques exist for studying protein aggregation, in silico methods have become invaluable due to their speed, cost-effectiveness, and adaptability. This chapter provides a concise overview of the decades-long development of computational tools aimed at identifying, quantifying, and exploring the aggregation propensity (AP) and kinetics of proteins and their variants. With a particular emphasis on the influence of protein mutations, we delve into the prediction of protein aggregation kinetics and the comprehension of the underlying mechanisms through molecular dynamic simulations.

More than 90 individual mutations in copper-zinc superoxide dismutase are associated with familial cases of amyotrophic lateral sclerosis and they are mostly fatal within one to five years of the onset of the disease. Results obtained from studies with transgenic mice, transfected cells, and patients suggest that familial amyotrophic lateral sclerosis copper-zinc superoxide dismutase mutants have gains or enhancements in one or more cytotoxic properties, which are not related to the superoxide dismutation activity. The proposed nature of the cytotoxic gain-of-function of the familial amyotrophic lateral sclerosis copperzinc superoxide dismutase mutants under debate includes enhanced free radical-generating (peroxidative) activity, enhanced activity of peroxynitrite-mediated tyrosine nitration, and familial amyotrophic lateral sclerosis mutant-associated aggregate formation due to failure of protein folding. We review these proposals and summarize our findings from the studies with purified familial amyotrophic lateral sclerosis copper-zinc superoxide dismutase mutants.