TY - JOUR
T1 - What is the role of protein aggregation in neurodegeneration?
AU - Ross, Christopher A.
AU - Poirier, Michelle A.
N1 - Funding Information:
C.A.R. and M.A.P. and the Huntington’s Disease Center are supported by the National Institute of Neurological Disease and Stroke, the National Institute of Ageing, the High-Q Foundation, the Huntington’s Disease Society of America and the Hereditary Disease Foundation. We thank R. Wetzel for detailed reading and comments on the manuscript and sharing data prior to publication, and C. Dobson, D. Rubinsztein, P. Lansbury, R. Kopito, S. Radford, E. Wanker, J. Kelly, M. Amzel and L. Ellerby for comments, discussions or the sharing of data. We also thank the participants of the I2CAM meeting on protein aggregation in Lausanne, Switzerland, July 2005, organized by H. Lashuel, for comments and suggestions, and the participants of the High Q workshop on aggregation organized by A. Tobin and E. Signer in New York, April 2005, for discussion.
Funding Information:
The authors are supported by the European Commission Framework Program 6 and the Russian Academy of Sciences for the programme in Molecular and Cell Biology (K.A.L., D.M.C. and S.L.), and the National Institute of General Medical Sciences and the National Institute on Drug Abuse (V.V.V.).
PY - 2005/11
Y1 - 2005/11
N2 - Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic. However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion. The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins. This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets.
AB - Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic. However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion. The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins. This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets.
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U2 - 10.1038/nrm1742
DO - 10.1038/nrm1742
M3 - Review article
C2 - 16167052
AN - SCOPUS:27644596641
SN - 1471-0072
VL - 6
SP - 891
EP - 898
JO - Nature Reviews Molecular Cell Biology
JF - Nature Reviews Molecular Cell Biology
IS - 11
ER -