Mutant ubiquitin expressed in Alzheimer's disease causes neuronal death

F. M.S. De Vrij, L. Gregori, D. F. Fischer, J. Verhaagen, E. M. Hol*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

120 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2680-2688
Number of pages9
JournalFASEB Journal
Issue number14
Publication statusPublished - 2001
Externally publishedYes


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