Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts

Polyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the coding region of specific genes. This leads to the production of pathogenic proteins containing critically expanded tracts of glutamines. Although polyQ diseases are individually rare, the fact that these nine diseases are irreversibly progressive over 10 to 30 years, severely impairing and ultimately fatal, usually implicating the full-time patient support by a caregiver for long time periods, makes their economic and social impact quite significant. This has led several researchers worldwide to investigate the pathogenic mechanism(s) and therapeutic strategies for polyQ diseases. Although research in the field has grown notably in the last decades, we are still far from having an effective treatment to offer patients, and the decision of which compounds should be translated to the clinics may be very challenging. In this review, we provide a comprehensive and critical overview of the most recent drug discovery efforts in the field of polyQ diseases, including the most relevant findings emerging from two different types of approaches-hypothesis-based candidate molecule testing and hypothesis-free unbiased drug screenings. We hereby summarize and reflect on the preclinical studies as well as all the clinical trials performed to date, aiming to provide a useful framework for increasingly successful future drug discovery and development efforts.Project ON.2 SR&TD Integrated Program (NORTE-07-0124-FEDER-000021), co-funded by North Portugal Regional Operational Program (ON.2-O Novo Norte), under the National Strategic Reference Framework, through the European Regional Development Fund (ERDF) and also supported by Fundação para a Ciência e Tecnologia through the project POCI-01-0145-FEDER-016818 (PTDC/NEU-NMC/3648/2014)info:eu-repo/semantics/publishedVersio

European radiation protection course: basics

Radiation protection is a major challenge in the industrial applications of ionising radiation, both nuclear and non-nuclear, as well as in other areas such as the medical and research domains. The overall objective of this textbook is to participate to the development of European high-quality scheme and good practices for education and training in radiation protection (RP), coming from the new Council Directive 2013/59/Euratom laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation. These ERPTS (European Radiation Protection Training Scheme) reflects the needs of the Radiation Protection Expert (RPE) and the Radiation Protection Officer (RPO), specifically with respect to the Directive 2013/59/Euratom in all sectors where ionising radiation are applied. To reflect the RPE training scheme, six chapters have been developed in this textbook: • Radioactivity and nuclear physics • Interaction of ionising radiation with matter • Dosimetry • Biological effects of ionising radiation • Detection and measurement of ionising radiation • Uses of sources of ionising radiation The result is a homogeneous textbook, dealing with the ERPTS learning outcomes suggested by ENETRAPII project (European Network on Education and Training in RAdiological Protection II) from the 7th Framework Programme. A cyberbook is also part of the whole training material to develop the concept of "learning more" (http://www.rpe-training.eu). The production of this first module "basics" training material, in the combined form of a textbook plus

Marquage au tritium specifique du residu tryptophanyle par oxydation enzymatique suivie d'une reduction stereoselective

SIGLECNRS T 55736 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc