Ribosome-tethered chaperones that interact with nascent polypeptide chains have been identified in both prokaryotic and eukaryotic systems. However, these ribosome-associated chaperones share no sequence similarity: bacterial trigger factors (TF) form an independent protein family while the yeast machinery is Hsp70-based. The absence of any component of the yeast machinery results in slow growt...

Histones, the structural unit of chromatin, must be assembled/dissembled to preserve or change chromatin organization in accordance to cellular needs. Initially, function of histone chaperones was thought to be only “histone carriers/vehicles”, but now with accumulating evidences they are known to be the key actors of histone metabolism. With this outburst of knowledge, histone chaperones are n...

A large number of neurodegenerative diseases in humans result from protein misfolding and aggregation. Protein misfolding is believed to be the primary cause of Alzheimer's disease, Parkinson's disease, Huntington's disease, Creutzfeldt-Jakob disease, cystic fibrosis, Gaucher's disease and many other degenerative and neurodegenerative disorders. Cellular molecular chaperones, which are ubiquito...

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the disease protein, huntingtin. In HD patients and transgenic mice, the affected neurons form characteristic ubiquitin-positive nuclear inclusions (NIs). We have established ecdysone-inducible stable mouse Neuro2a cell lines that express truncated N-terminal huntingtin (tNhtt) wit...

What is a chaperone in the context of pharmacology? The term chaperone is borrowed from the name of a class of proteins that function in living cells [1]. Protein molecules are usually only marginally stable under physiological conditions, so some percent of them are often unfolded or misfolded. Such molecules can aggregate with one another, or with properly functioning proteins, with deleterio...

The folding of newly synthesized proteins and the maintenance of pre-existing proteins are essential in sustaining a living cell. A network of molecular chaperones tightly guides the folding, intracellular localization, and proteolytic turnover of proteins. Many of the key regulators of cell growth and differentiation have been identified as clients of molecular chaperones, which implies that c...

Background & Aims: Today, diabetic nephropathy is considered to be one of the most common causes of end stage renal disease. Uncontrolled hyperglycemia, and consequently, production of advanced glycation end products activate pathways which play key roles in diabetic nephropathy. Among these pathways, high expression of receptor for advanced glycation end products (RAGE) and transforming growth...