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First published online May 20, 2009
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Amyloid-β peptide (Aβ) is a normal metabolite produced in neurons, but its oligomeric form is toxic and has been associated with neurodegenerative disorders such as Alzheimer's disease. Studies of transgenic worms have shown that heat-shock proteins (HSPs) can interact with and detoxify Aβ, but how this occurs in mammals was unknown. On page 1917, Seong-Tshool Hong and colleagues characterise a new role for Omi – a mammalian HSP with pro-apoptotic function – in detoxifying Aβ in mouse neurons. Using confocal microscopy, they show that Omi and Aβ colocalise in the mitochondria and ER; in addition, Omi interacts preferentially with the most toxic oligomeric form of Aβ. Rather than causing the degradation of Aβ, Omi induces its disaggregation and inhibits the secretion of Aβ from neurons, which decreases the level of toxic Aβ and might reduce Aβ stress in the brain. Interestingly, the association of Omi with Aβ also inhibited the pro-apoptotic actions of Omi, suggesting a mutual detoxification of these two proteins in neurons. These results are in line with previous findings that Omi-knockout mice suffer from a fatal neurodegenerative disorder, and open up the possibility that this Omi-dependent Aβ-detoxification pathway is a promising therapeutic target for Alzheimer's disease and other neurodegenerative disorders.
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