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Mutant ubiquitin expressed in Alzheimer’s disease causes neuronal death

Onderzoeksgroep Verhaagen
Publicatiejaar 2001
Gepubliceerd in FASEB Journal
Auteur(s) Femke M S de Vrij, J.A. Sluijs, L Gregori, D.F. Fischer, W.T.J.M.C. Hermens, D Goldgaber, J. Verhaagen, F.W. van Leeuwen, E.M. Hol

Ubiquitin-B+1 (UBB+1) is a mutant ubiquitin that accumulates in the neurones of patients with Alzheimer’s disease (AD). Here we report on the biochemical and functional differences between ubiquitin and UBB+1 and the effect of the mutant protein on neuronal cells. UBB+1 lacks the capacity to ubiquitinate, and although it is ubiquitinated itself, UBB+1 is not degraded by the ubiquitin-proteasomal system and is quite stable in neuronal cells. Overexpression of UBB+1 in neuroblastoma cells significantly induces nuclear fragmentation and cell death. Our results demonstrate that accumulation of UBB+1 in neurones is detrimental and may contribute to neuronal dysfunction in AD patients.

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