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Alzheimer’s disease (AD) is a neurological disorder characterized by the presence of amyloidb(Ab) peptide fibrils and oligomers in the brain. It has been suggested that soluble Ab oligomers, rather than Ab fibrils, contribute to neurodegeneration and dementia due to their higher level of toxicity. | ễFEBS Journal Formation of highly toxic soluble amyloid beta oligomers by the molecular chaperone prefoldin Masafumi Sakono1 Tamotsu Zako1 Hiroshi Ueda2 Masafumi Yohda3 and Mizuo Maeda1 1 Bioengineering Laboratory RIKEN Institute Saitama Japan 2 Department of Chemistry and Biotechnology Schoolof Engineering The University of Tokyo Japan 3 Department of Biotechnology and Life Science Tokyo University of Agriculture and Technology Japan Keywords Alzheimer s disease amyloid b molecular chaperone prefoldin soluble oligomers Correspondence T. Zako Bioengineering Laboratory RIKEN Institute 2-1 Hirosawa Wako Saitama 351 0198 Japan Fax 81 48 462 4658 Tel 81 48 467 9312 E-mail zako@riken.jp M. Maeda Bioengineering Laboratory RIKEN Institute 2-1 Hirosawa Wako Saitama 351 0198 Japan Fax 81 48 462 4658 Tel 81 48 467 9312 E-mail mizuo@riken.jp Present address PRESTO Japan Science and Technology Agency Saitama Japan Received 16 June 2008 revised 5 September 2008 accepted 3 October 2008 Alzheimer s disease AD is a neurological disorder characterized by the presence of amyloid b Ab peptide fibrils and oligomers in the brain. It has been suggested that soluble Ab oligomers rather than Ab fibrils contribute to neurodegeneration and dementia due to their higher level of toxicity. Recent studies have shown that Ab is also generated intracellularly where it can subsequently accumulate. The observed inhibition of cytosolic proteasome by Ab suggests that Ab is located within the cytosolic compartment. To date although several proteins have been identified that are involved in the formation of soluble Ab oligomers none of these have been shown to induce in vitro formation of the high-molecular-mass 50 kDa oligomers found in AD brains. Here we examine the effects of the jellyfish-shaped molecular chaperone prefoldin PFD on Ab 1-42 peptide aggregation in vitro. PFD is thought to play a general role in de novo protein folding in archaea and in the biogenesis of actin tubulin and possibly .
