New Hot Paper Comment by Professor Christopher M. Dobson

Professor Christopher M. Dobson answers a few questions about this month's new hot paper in the field of Multidisciplinary.

From •>>July 2003

Field: Multidiciplinary
Title: "Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases"
Author: Bucciantini, M;Giannoni, E;Chiti, F;Baroni, F;Formigli, L;Zurdo, JS;Taddei, N;Ramponi, G;Dobson, CM;Stefani, M
Journal: NATURE, 416: (6880) 507-511 APR 4 2002
Addresses:
Univ Florence, Dipartimento Sci Biochim, Viale Morgagni 50, I-50134 Florence, Italy.
Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy.
Univ Florence, Dipartimento Anat Istol & Med Legale, I-50134 Florence, Italy.
Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.

  Why do you think your paper is highly cited?

I think it helps to bring together a lot of characteristics of "misfolding diseases" and offers the basis for a general and fundamental understanding of these increasingly common and debilitating conditions.

  Does it describe a new discovery or new methodology that's useful to others?

I hope it will prompt a lot of people interested in protein folding in vitro to try to relate their work to efforts to understand disease.

  Could you summarize the significance of your paper in layman's terms?

We have previously shown that the ability to form protein aggregates, known as amyloid fibrils, that are normally associated with just a few proteins involved in conditions such as Alzheimer's Disease or the transmissible spongiform encephalopathies (including vCJD) may be a common or "generic" feature of all our proteins. This paper suggests that the species which form initially during the conversion of a normally soluble protein to the amyloid form may be generally toxic to cells. Taken together these results support the idea that these diseases—many of which are primarily associated with aging—fundamentally result from the loss of the regulating or "housekeeping" functions of living organisms rather than from some specific aberrant conformational properties of the proteins associated with these diseases.
Visit the ESI Special Topic: Alzheimer's Disease.

  How did you become involved in this research?

We have long been interested in understanding the mechanism of protein folding, and more recently in how and why proteins can fail to fold or to remain properly folded. The recognition that these events were linked to some of the most debilitating and common human diseases prompted us to focus much of our efforts in this area of research.

Professor Christopher M. Dobson
University of Cambridge
Dept. of Chemistry
Cambridge, UK
This paper was most recently featured in Emerging Research Fronts - December 2002.
Read comments by this new hot paper's co-author Prof. Massimo Stefani.

ESI Special Topics, July 2003
Citing URL - http://www.esi-topics.com/nhp/2003/july-03-ChristopherMDobson.html