Future Science OA Special Issue Explores Current Protein Misfolding Disease Research Info CF, Other Diseases

Future Science OA Special Issue Explores Current Protein Misfolding Disease Research Info CF, Other Diseases

Future Science Group (FSG), a progressive publisher focused on breakthrough medical, biotechnological, and scientific research, has announced publication of a special issue in Future Science OA, covering the rapidly evolving field of protein misfolding diseases — a category that includes Cystic Fibrosis, Alzheimer’s and Parkinson’s Diseases, which are rising in incidence, creating an increasing financial and healthcare burden on society, with effective treatments and accurate diagnostics for these diseases posing a significant unmet need.

This special Open Access edition of Future Science OA (Vol. 1, No. 2 , DOI 10.4155/fso.15.38), features Guest Editor Salvador Ventura, a Professor in the Department of Biochemistry and Molecular Biology and leader of the Protein Folding and Conformational Diseases group at Universitat Autnoma de Barcelona, Spain. The issue’s content highlights recent advances in scientific understanding of protein misfolding disorders and profiles fresh ideas for future therapies in a series of articles written by experts at the cutting edge of the field.

The issue kicks off by examining recent inroads being made in expanding knowledge of protein misfolding disorders and their protein targets, then turns focus on amyloid aggregation in specific disease areas, including the neurodegenerative disorders Alzheimer’s, Parkinson’s and Huntingdon’s Diseases; glioblastoma; cystic fibrosis; spinal and bulbar muscular atrophy; and malaria.

“This special issue is timely, as the social and economical burden associated with the protein misfolding disorders is steadily increasing in our aging society,” explains Dr. Ventura. “Accordingly, understanding the molecular mechanisms underlying these diseases is becoming extremely urgent.

In a preface to the special issue (Future Science OA Vol. 1, No. 2 , DOI 10.4155/fso.15.38), Prof. Ventura observes that regrettably the mechanisms responsible for toxicity of protein aggregates are still not completely understood, and the number of protein targets whose misfolding and aggregation is being shown to be associated with the onset of pathologic conditions is constantly increasing. He notes that since development of degenerative disorders is expected to increase at a similar rate with life expectancy, it is likely that in years to come misfolding diseases will become more common and prevalent than had previously been thought. Consequently he says we should be prepared to deal with such a dramatic scenario and support research efforts to understand the molecular mechanism that underlies these devastating disorders without further delay.

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This special Future Science OA issue illustrates how protein misfolding is intimately linked to both health and disease and collects our more recent knowledge on the molecular causes behind deleterious misfolding reactions. This information is paving the way for the development of novel and effective therapeutic strategies to tackle these devastating pathologies.

“Many human diseases are associated with protein misfolding. With the rising burden of these diseases, it is important to advance understanding into why cellular protein processing goes awry, and to discover and utilize targets to improve diagnostic therapy,” comments Francesca Lake, Managing Editor. “This issue is intended to provide a snapshot of where we are today, and provide a thought-proving look at the future of this field.”

In an outline of his lab research team’s investigational focus,Professor Ventura, explains that proteins are involved in virtually every biological process, and in order to function, these chains must fold into the unique three-dimensional structure that is characteristic for each protein. And since proteins almost never act in an isolated manner, and mostly interact with other proteins in order to perform essential roles in many important cellular processes, protein malfunction is often related to disease, with thousands disease-related proteins having been identified to date. Dr. Ventura observes that In many instances, these disorders are the outcome of a failure in their folding process and/or in their binding to one or more protein partners.

Dr. Ventura’s research group works in three main research areas associated with protein folding:

• Folding of Disulfide-Rich Proteins
The investigators exploit the particular chemistry of disulfide bonds to characterize the folding of disulfide-rich proteins, with results that illustrate a high diversity of folding mechanisms, and by combining kinetic studies with the structural determination of folding intermediates, they have provided new molecular clues in oxidative folding and clarified some of the major rules that govern it.

• Folding of Cell Signaling Domains
Intracellular signaling networks controls cellular behavior, and are assembled through the interactions of proteins with one another, and with other molecules. Typically, protein interaction domains are independently folding modules that can be expressed in isolation from their host proteins while retaining their intrinsic ability to bind their physiological partners. After establishing the SH3 domain as a consistent model for the study of protein folding and binding, Prof. Ventura’s team plan to expand their activity to other cell signaling domains, noting that understanding how the proteins fold and bind is of paramount importance since many human disorders result from breakdowns in protein binding and signal transduction.

• Protein Misfolding and Aggregation

The researchers are interested in disease-related misfolding and amyloid fibril assembly, and have shown using in vitro models that amyloid formation depends on specific short amino acid stretches, opening a door for prediction of therapeutically relevant regions in amyloid proteins. These regions are usually protected inside the protein globular structure, suggesting a selection against aggregation during evolution. Using this information, the team have developed AGGRESCAN, a software for the prediction of protein aggregation propensity (http://bioinf.uab.es/aggrescan/). By integrating computational and experimental approaches they are studying the relationship between the sequence and structural properties of the aggregated and toxic states of several amyloid proteins, including prions, IAPP and A peptide.

The investigators have established bacteria as a simple cellular model to study in vivo protein aggregation, and demonstrated the formation in prokaryotes of oligomers and amyloid structures through selective interactions. This suggests evolutionary conserved strategies to avoid the harmful effects of protein aggregation by sequestering sticky folding intermediates into stable aggregated structures in both eukaryotes and bacteria. The researchers are now using proteomic and genomic approaches to explore the sequential and structural determinants of amyloid formation inside eukaryotic cells using yeast as a model.

The full special issue content can be found at:
http://www.future-science.com/toc/fso/1/2

Sources:
Future Science OA
Future Science Group
Institute of Biotechnology & Biomedicine, Department of Biochemistry & Molecular Biology, Parc de Recerca UAB, Mdul B, Universitat Autnoma de Barcelona, Barcelona, Spain

Image Credits:
Future Science Group
OMICS International
Institute of Biotechnology & Biomedicine, Department of Biochemistry & Molecular Biology, Parc de Recerca UAB, Mdul B, Universitat Autnoma de Barcelona, Barcelona, Spain

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