From Alzheimer to Huntington: Why is a Structural Understanding So Difficult?

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2003 Jan 30

PMID 12554637

Citations 44

Authors

Piero Andrea Temussi

Laura Masino

Annalisa Pastore

Affiliations

Soon will be listed here.

Abstract

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.

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