Editorial [Hot Topic: Therapeutic Use of Heat Shock Proteins and Essential Factors in Prognosis, Diagnosis and Treatment of Neurodegenerative and Metabolic Diseases (Guest Editor: Yusuf Tutar)]

A functional protein must be in its specific three dimensional native structure. All information to reach to the native state is ciphered in its amino acid sequence. However the milieu of a cell as well as stress factors presents challenges for folding to native state [1-3]. Several stress factors i.e. temperature elevation, pH, salinity and oxygen concentration alteration, ageing may influence cells and protein folding. Fortunately, heat shock proteins (Hsps) help misfolded or unfolded proteins for proper folding. Protein quality check provides protein homeostasis and Hsps play essential role during these biochemical processes [4,5]. If Hsp cannot help substrate protein then it send the substrate to lysozyme for degradation. Uncontrolled protein folding may lead aggregation and eventually several diseases including Huntington, Alzheimer, Parkinson, Creutzfeldt-Jakob, cystic fibrosis, Gaucher and other polyglutamine neurodegenerative diseases [6-8]. Several different types of heat shock proteins or combination of these proteins have been employed as therapeutic agent since stress factors increase levels of denatured proteins. This theme issue focuses on treatment of neurodegenerative and metabolic diseases through heat shock proteins [3,7,8]. The first paper gives a brief summary on major Hsp families Hsp70, Hsp40, Hsp90, Hsp100, Hsp60, nucleotide exchange factors and small Hsps. The paper by Dr. Soti reports an interesting topic. The paper presents diet and metabolic stress related heat shock response and treatment. Small Hsps (sHsps) are the least popular group among Hsp family. Like other Hsps, sHsps confer thermotolerence to proteins in cellular extracts. The most distinguishing property of Hsps is their ATP-independent function as molecular chaperones [1]. Dr. Laskowska presents properties and diversity of sHsps along with their roles in cancer, neurodegenerative and protein folding diseases. The biggest problem in cellular milieu is macromolecular crowding. Protein-protein interaction in this environment may lead to aggregation. The process first forms small seeds and small seeds eventually forms fibers [4,5]. Aggregation of different types of protein cause various neurodegenerative diseases. Hsps prevent aggregation and solubilise aggregates, therefore Hsps have potential roles as suppressors and therapeutic agent [3-5]. Dr. Arawaka use alpha-synuclein as model to explain Hsps roles in neurodegenerative diseases. The famous Trojan horse tale provided a unique idea for researchers for cell-penetrating peptide technology. The technology of combining Hsps action with cell-penetration applied to several biochemical process, i.e apoptosis, neurodegenerative diseases [3]. A contemporary approach of these applications provided by Dr. Dietz. By the same Trojan analogy cell walls serve as rampart and the only way for cell to communicate outside environment is by means of special gates; ion-channels. Therefore, cell signaling cascades via these channels may help our understanding of diseases. Dr. Schneider reviewed role of Hsp interactions with the channels and their potential therapeutic consequences. Protein homeostasis depends on a fine equilibrium between protein synthesis and protein degradation. Heat shock proteins play essential roles in substrate protein degradation. At the later stage of life protein degradation function decreases. As a result of wasted protein and misfolded protein accumulation, protein aggregation leads neurodegenerative diseases [5-8]. Dr. Lee gathered Hsp roles in degradation pathways associated with neurodegenerative diseases. Proteins are essential tools for an organism function therefore protein homeostasis is essential for metabolism continuity. Since Hsp help nascent protein and misfolded protein folding to reach their functional three dimensional state, an increase in Hsp concentration may prevent protein aggregation and solubilise aggregates [7,8]. One strategy to increase Hsp concentration is induction. This strategy used as therapeutic approach for neurodegenerative diseases and Dr. Nagai gathered information for the polyglutamine neurodegenerative diseases. Similarly, Dr. Wyttenbach investigates Hsps as drug targets for chronic neurodegeneration. Hsp modulation, drug delivery and side effects were discussed in detail. Currently, therapeutic use of Hsps as molecular chaperones to cure neurodegenerative disease is at the earlier stage however researchers give promising results for future efforts.