. Structural basis of E2-25K/UBB+1 interaction leading to proteasome inhibition and neurotoxicity. J Biol Chem. 2010 Nov 12;285(46):36070-80. PubMed.

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  1. Time for the Ubiquitin-Proteasome System #4

    Misframed ubiquitin (UBB+1) accumulates in tauopathies and in polyglutamine diseases, but not in synucleinopathies. Over the last decade, much information about this endogenous proteasome inhibitor has become available; it is dose-dependently toxic and impairs hippocampal-related contextual memory.

    Ko et al. provide a firm structural basis for an interaction between the E2 enzyme (E2-25K), via its UBA domain, and UBB+1, leading to proteasome inhibition in relation to Aβ neurotoxicity and neuronal cell death.

    They anticipate that their work will lead to the discovery of new approaches to the treatment of Alzheimer and Huntington diseases and related disorders.