Seminars Archive

What structural biology can tell us about neurodegenerative diseases

Abstract
An increasing number of neurodegenerative pathologies, which include Alzheimer\'s, Parkinson\'s and Huntington\'s diseases, prion encephalopathies, and cystic fibrosis, have been associated with protein aggregation and misfolding [1]. Among them is the family of diseases caused by anomalous expansion of polyglutamines, which is interesting both for its specificity of genetic transmission and for the generality of the structural issues involved. We have chosen this family as a paradigmatic example to approach misfolding diseases and studied them by a combination of biophysical techniques. We aim both at understanding the aggregation properties of the pathological species and at rationalising the function of the non-pathological forms. In my talk, I shall review the field of aggregation and illustrate in detail the specific example of how structural studies may provide a powerful tool to approach polyglutamine diseases and, more in general, misfolding diseases. 1. Temussi, P.A., Masino L.and Pastore A. From Alzheimer to Huntington: why is a structural understanding so difficult? EMBO J. 22, 355-361 (2003)