Functionally active cross-linked protein oligomers formed by homocysteine thiolactone.

Deposition of high-order protein oligomers is a common hallmark of a large number of human diseases and therefore, has been of immense medical interest. From the past several decades, efforts are being made to characterize protein oligomers and explore how they are linked with the disease pathologies. In general, oligomers are non-functional, rather cytotoxic in nature while the functional (non-cytotoxic) oligomers are quite rare.

TMAO to the rescue of pathogenic protein variants.

Trimethylamine N-oxide (TMAO) is a chemical chaperone found in various organisms including humans. Various studies unveiled that it is an excellent protein-stabilizing agent, and induces folding of unstructured proteins. It is also well established that it can counteract the deleterious effects of urea, salt, and hydrostatic pressure on macromolecular integrity.

The gut metabolite, trimethylamine N-oxide inhibits protein folding by affecting cis-trans isomerization and induces cell cycle arrest.

Trimethylamine N-Oxide (TMAO) is an important metabolite, which is derived from choline, betaine, and carnitine in various organisms. In humans, it is synthesized through gut microbiota and is abundantly found in serum and cerebrospinal fluid (CSF). Although TMAO is a stress protectant especially in urea-rich organisms, it is an atherogenic agent in humans and is associated with various diseases.

Brain Metabolite, N-Acetylaspartate Is a Potent Protein Aggregation Inhibitor.

Deposition of toxic protein inclusions is a common hallmark of many neurodegenerative disorders including Alzheimer's disease, Parkinson disease etc. N-acetylaspartate (NAA) is an important brain metabolite whose levels got altered under various neurodegenerative conditions. Indeed, NAA has been a widely accepted biological marker for various neurological disorders.

N-Acetylaspartate Is an Important Brain Osmolyte.

Most of the human diseases related to various proteopathies are confined to the brain, which leads to the development of various forms of neurological disorders. The human brain consists of several osmolytic compounds, such as N-Acetylaspartate (NAA), myo-inositol (mI), glutamate (Glu), glutamine (Gln), creatine (Cr), and choline-containing compounds (Cho). Among these osmolytes, the level of NAA drastically decreases under neurological conditions, and, hence, NAA is considered to be one of the most widely accepted neuronal biomarkers in several human brain disorders.

Osmolytes in vaccine production, flocculation and storage: a critical review.

Small molecule osmolytes, responsible for protecting stresses have long been known to rescue proteins and enzymes from loss of function. In addition to protecting macromolecules integrity, many osmolytes also act as potential antioxidant and also help to prevent protein aggregation, amyloid formation or misfolding, and therefore are considered promising molecules for neurodegenerative and many other genetic diseases. Osmolytes are also known to be involved in the regulation of several key immunological processes.