MRC National Institute for Medical Research, London
Science for Health
Annalisa Pastore group
Understanding the molecular bases of neurodegeneration
Our main line of research concerns the study of proteins involved in neurodegenerative processes of the central nervous system, with the ultimate aim of understanding the causes of pathology and developing new theurapeutic strategies. We are addressing the problem by studying the function/structure relationship of the non-pathologic forms of the proteins involved, and by investigating the mechanisms which lead to neurodegeneration, such as protein misfolding, aggregation, and misfunctioning.
The families of diseases we focus on involve dominant and recessive ataxias, such as Joseph-Machado disease and Friedreich’s ataxia. We are also investigating the bases of intelligence through studying what leads to Fragile X mental retardation syndrome.
To carry out our studies, we use biophysical, biochemical, and bioinformatics techniques, which range from different spectroscopies, calorimetry, molecular dymamics and comparative modelling. We use advanced Nuclear Magnetic Resonance techniques to determine the structure and dynamics of the protein we are interested in.
Click image to view at full-size
The structure of frataxin and a model of its cellular role. Frataxin is an iron dependent inhibitor of the enzymatic activity of the desulphurase IscS, the protein responsible for formation of iron sulfur cluster formation on the transient acceptor IscU.
Selected publications
- Adinolfi, S; Iannuzzi, C; Prischi, F; Pastore, C; Iametti, S; Martin, SR; Bonomi, F and Pastore, A (2009)
Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS.
Nature Structural & Molecular Biology 16, 390-396 PubMed abstract - Sanfelice, D; Tancredi, T; Politou, A; Pastore, A and Temussi, PA (2009)
Cold denaturation and aggregation: a comparative NMR study of titin I28 in bulk and in a confined environment.
Journal of the American Chemical Society 131, 11662-11663 PubMed abstract - Zen, A; de Chiara, C; Pastore, A and Micheletti, C (2009)
Using dynamics-based comparisons to predict nucleic acid binding sites in proteins: an application to OB-fold domains.
Bioinformatics 25, 1876-1883 PubMed abstract - Adrover, M; Pauwels, K; Pringent, S; de Chiara, C; Xu, Z; Chapuis, C; Pastore, A and Rezaei, H (2010)
Prion fibrillization is mediated by a native structural element which comprises the helices H2 and H3.
Journal of Biological Chemistry 285, 21004-21012 PubMed abstract
Our research themes
Click links to view others working on these themes
© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA
Top of page