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From Alzheimer to Huntington: why is a structural understanding so difficult?
Author(s) -
Temussi Piero Andrea,
Masino Laura,
Pastore Annalisa
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg044
Subject(s) - biology , protein folding , neuroscience , mechanism (biology) , protein aggregation , huntington's disease , alzheimer's disease , neurodegeneration , disease , computational biology , bioinformatics , genetics , microbiology and biotechnology , medicine , philosophy , epistemology , pathology
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.