Biomedical implications of protein folding and misfolding.

A review of protein-folding mechanisms is presented to indicate (i) the formation of correctly folded and misfolded forms, and (ii) the biomedical implications involved. Protein mechanisms may be classified into series and series-parallel mechanisms. The mechanism may involve one or more stable intermediate (partially folded, misfolded, with some structure) states. It is the parallel or the 'off-pathway' step(s) that lead to the aggregate (misfolded state). This aggregate state yields the amyloid deposits in human tissue that lead to diseases in humans that are resistant to treatment. Means by which the off-pathway step may be minimized and the correct folding pathway enhanced are presented. Particular emphasis is placed on the in vivo machinery (chaperones) that is in place in the cells, and how it functions to allow the proteins to fold in the correct and active form, thus minimizing the amyloid deposits in tissues. More effort needs to be placed to understand the function of these chaperones, and thus help facilitate the formation of active and stable proteins in the cells. Though more effort needs to be placed in the present treatment strategies, novel treatment procedures also need to be explored in order to develop effective strategies to treat these seemingly intractable diseases.

Duke Scholars

Author Tuan Vo-Dinh Biomedical Engineering