NR ANGG
AU Temussi,P.A.; Masino,L.; Pastore,A.
TI From Alzheimer to Huntington: why is a structural understanding so difficult?
QU EMBO Journal 2003 Feb 3; 22(3): 355-61
PT journal article, NEW EMBO MEMBER'S REVIEW
AB An increasing family of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, prion encephalopathies and cystic fibrosis is associated with aggregation of misfolded polypeptide chains which are toxic to the cell. Knowledge of the three-dimensional structure of the proteins implicated is essential for understanding why and how endogenous proteins may adopt a non-native fold. Yet, structural work has been hampered by the difficulty of handling proteins insoluble or prone to aggregation, and at the same time that is why it is interesting to study these molecules. In this review, we compare the structural knowledge accumulated for two paradigmatic misfolding disorders, Alzheimer's disease (AD) and the family of poly-glutamine diseases (poly-Q) and discuss some of the hypotheses suggested for explaining aggregate formation. While a common mechanism between these pathologies remains to be proven, a direct comparison may help in designing new strategies for approaching their study.
AD National Institute for Medical Research, Medical Research Council, The Ridgeway, Mill Hill, London NW7 1AA, UK and Department of Chemistry, University of Naples 'Federico II', Via Cinthia 45, I 80126 Naples, Italy Corresponding authors e-mail: pat@chemistry.unina.it or apastor@nimr.mrc.ac.uk
SP englisch