Human Molecular Genetics, Vol 8, 2451-2459, Copyright © 1999 by Oxford University Press
T Rich, E Assier, J Skepper, HB Segard, RL Allen, D Charron and J Trowsdale
Spinocerebellar ataxias and Huntington's disease are examples of
neurodegenerative diseases caused by a trinucleotide repeat expansion. One
hallmark of such diseases is the formation of inclusion bodies (IBs) within
neuronal tissue. Although these inclusions may play a pivotal role in the
disease process, the reasons underlying their specific accumulation remain
obscure. By studying intranuclear IBs in dividing cells we demonstrate for
the first time that inclusions such as those of ataxin-1 disperse during
mitosis, thus reducing the nuclear aggregate burden. IBs reform in the
interphase nucleus. By high- resolution confocal microscopy we also show
that inclusions comprise ordered structures capable of homotypic
interactions. Unlike those of a non-pathologic protein, ataxin-1 inclusions
were shown to be capable of non-specific protein sequestration. Our studies
indicate that the specific accumulation of inclusions in terminally
differentiated cells such as neurons is a direct consequence of their
inability to divide and therefore provides a key to explaining their
persistence in neurodegenerative disease.
ARTICLES
Disassembly of nuclear inclusions in the dividing cell-a novel insight into neurodegeneration
Department of Pathology, Division of Immunology, University of Cambridge, Cambridge CB2 1QP, UK,
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