Dottorato in Medicina e Terapia Sperimentale: "Chaperonopathies: a new field in Biology and Medicine"
Academic year 2014/2015
- Teaching staff
- Prof. Maurizio Parola (Moderatore)
Prof. Giuseppe Poli (Coordinatore)
- Degree course
- Ciclo XXVII
- Teaching period
- --- Nuovo Ordinamento ---
- da 0 a 5
Sommario del corso
venerdì 12 giugno 2015
"Chaperonopathies: a new field in Biology and Medicine"
By Alberto J. L. Macario, M.D., and Everly Conway de Macario, Ph.D.
The molecular chaperones, co-chaperones, and chaperone co-factors constitute the chaperoning system present in various degrees of complexity in all organisms, uni- and multicellular across the three evolutionary Domains of life. Components of this system, some of which are also known as heat-shock proteins (Hsp), are involved in protein homeostasis and other cellular processes: i.e., they have two categories of functions, canonical and non-canonical, with the latter unrelated to protein quality control. Lately, it has become evident that chaperones can also cause diseases by defect, excess, or mistake, grouped under the name of chaperonopathies. The defects in chaperonopathies can be better understood by visualizing the chaperone molecule as an assembly of functional modules. Alterations in any of these modules by mutation or post-translational modification can change or abrogate its function and that of the entire molecule. This realization has provided new insights in various areas of Biology, Pathology, and Medicine. Most importantly, it has opened new avenues for therapeutics, in which chaperones become remedies or target for remedies. If a chaperone is non-functional or miss-functional it may be boosted with a chemical compound or replaced with the functional equivalent protein or its gene (positive chaperonotherapy), whereas if it is an etiologic-pathogenic factor it can be eliminated or blocked (negative chaperonotherapy). The basic mechanisms of the most common chaperonopathies will be briefly explained. The impact of mutations or post-translational modifications on the intrinsic molecular properties of chaperones is poorly understood. We have focused on the chaperonin-containing TCP-1 polypeptide (CCT), which in humans is constituted of eight different subunits that form octameric rings that associate in pairs forming hexadecamers. A mutation in the CCT5 subunit has been identified that causes disease. We have investigated the impact of this mutation on the subunit and oligomer intrinsic properties and illustrative results will be presented to show how these studies may be carried out. The era of chaperone pathology has begun with great promise for science and practical medicine. Reference: The Chaperonopathies. Diseases with defective molecular chaperones. http://www.springer.com/biomed/book/978-94-007-4666-4
Dept. Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore, and IMET, Columbus Center, Baltimore, MD, USA
Suggested readings and bibliography
Giorni Ore Aula Venerdì 14:30 - 16:00 Aula Seminari Polo Didattico Orbassano Lezioni: dal 12/06/2015 al 12/06/2015