NEW EMBO MEMBER'S REVIEW: From Alzheimer to Huntington: why is a structural understanding so difficult?
Open Access
- 3 February 2003
- journal article
- review article
- Published by Springer Nature in The EMBO Journal
- Vol. 22 (3) , 355-361
- https://doi.org/10.1093/emboj/cdg044
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.Keywords
This publication has 63 references indexed in Scilit:
- Alzheimer's disease and Down's syndrome: Sharing of a unique cerebrovascular amyloid fibril proteinPublished by Elsevier ,2004
- Stimulation of Enveloped Virus Infection by β-Amyloid FibrilsJournal of Biological Chemistry, 2002
- Proteases Acting on Mutant Huntingtin Generate Cleaved Products that Differentially Build Up Cytoplasmic and Nuclear InclusionsPublished by Elsevier ,2002
- Aβ42-positive non-pyramidal neurons around amyloid plaques in Alzheimer's diseaseThe Lancet, 2000
- Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: Implications for Huntington’s disease pathologyProceedings of the National Academy of Sciences, 1999
- Solution structures of micelle-bound amyloid β-(1-40) and β-(1-42) peptides of Alzheimer’s disease 1 1Edited by P. E. WrightJournal of Molecular Biology, 1999
- Common core structure of amyloid fibrils by synchrotron X-ray diffraction 1 1Edited by F. E. CohenJournal of Molecular Biology, 1997
- Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in BrainScience, 1997
- Polar zippersCurrent Biology, 1993
- Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid proteinBiochemical and Biophysical Research Communications, 1984