Creutzfeldt-Jakob Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Creutzfeldt-Jakob Disease, including details on mad cow disease, symptoms, causes, variants.

The alternative role of 14-3-3 zeta as a sweeper of misfolded proteins in disease conditions.

Kaneko K, Hachiya NS

Second Department of Physiology, Tokyo Medical University, 6-1-1 Shinjuku, Tokyo 160-8402, Japan.

Here, we propose a novel hypothesis that 14-3-3 zeta might act as a sweeper of misfolded proteins by facilitating the formation of aggregates, which are referred to as inclusion bodies. Studies on the localization of the 14-3-3 proteins in different types of inclusion bodies in the brain including neurofibrillary tangle in Alzheimer's disease, pick bodies in Pick's disease, Lewy body-like hyaline inclusions in sporadic amyotrophic lateral sclerosis, prion/florid plaques in sporadic/variant Creutzfeldt-Jakob disease, nuclear inclusions in spinocerebellar ataxia-1, and possibly Lewy bodies in Parkinson's disease suggest a close association of these diseases with 14-3-3 zeta. The highly conserved hydrophobic surface of the amphipathic groove in 14-3-3 zeta represents a general mechanism with diverse cellular proteins, and it may also allow for the molecular recognition of misfolded proteins by hydrophobic interaction in disease conditions. When the abnormal processing of misfolded proteins overwhelms the quality control systems of the cell, it is likely that 14-3-3 zeta is recruited to form deposits of protein aggregates with nonnative, misfolded proteins in order to protect the cell against toxicity. Hence, 14-3-3 zeta may be considered as an auxiliary therapeutic tool in the protein aggregation disorders.

Published 6 March 2006 in Med Hypotheses.
Full-text of this article is available online (may require subscription).

© 2005-2008 Creutzfeldt-Jakob Disease Research Today. All Rights Reserved.