Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: A work in progress

Department of Pathology, The Ottawa Hospital, University of Ottawa, and Cancer Research Program, The Ottawa Health Research Institute, Ottawa, Canada.
Neuropathology and Applied Neurobiology (Impact Factor: 3.93). 03/2007; 33(1):2-42. DOI: 10.1111/j.1365-2990.2006.00819.x
Source: PubMed


Neurodegenerative diseases are characterized pathologically by the abnormal accumulation of pathogenic protein species within the cell. Several neurodegenerative diseases feature intranuclear protein aggregation in the form of intranuclear inclusion bodies. Studies of these intranuclear inclusions are providing important clues regarding the cellular pathophysiology of these diseases, as exemplified by recent progress in defining the genetic basis of a subset of frontotemporal dementia cases. The precise role of intranuclear inclusion bodies in disease pathogenesis is currently a focus of debate. The present review provides an overview of the diverse family of neurodegenerative diseases in which nuclear inclusions form part of the neuropathological spectrum. In addition, current pathogenetic concepts relevant to these diseases will be reviewed and arguments for and against a protective role for intranuclear inclusions will be presented. The relationship of pathological intranuclear inclusions to functional intranuclear bodies will also be discussed. Finally, by analogy with pathological intranuclear inclusions, I will speculate on the possibility that intranuclear protein aggregation may represent a constitutive cellular protective mechanism occurring in neurons under physiological conditions.

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Available from: John Woulfe, May 21, 2014
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    • ", 2011 ) . The suggestion that nuclear aggregates , containing molecular chaperones and proteasome , can prevent the induction of CD ( Woulfe , 2007 ) was confirmed by the identification of a proteolytic activity in nuclear foci ( Iwata et al . , 2005 ; Rockel et al . "
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    • "Immunohistochemically, the inclusions are immunopositive for ubiquitin (Ub) and ubiquitin-related proteins (SUMO-1 and p62), while inclusions are less often immunolabeled with anti-polyglutamine antibody 1C2 [5] [6] [7] [8] [9] [10]. Recently , it has been reported that NII and GII are immunoreactive for fused in sarcoma (FUS) [11] [12]. "
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    • "It is well established that exposed hydrophobicity can lead to deleterious protein aggregation (Chiti, 2006). The nucleus in particular is highly susceptible to aggregation, as evidenced by the many human disorders associated with nuclear aggregation (Woulfe, 2007). From an evolutionary perspective, it is not surprising then that exposed hydrophobicity is the specific structural abnormality recognized by San1. "
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