Authors: Jake B Guinto Gillian P Ritson J Paul Taylor Mark S Forman
Publish Date: 2007/04/25
Volume: 114, Issue: 1, Pages: 55-61
Abstract
Frontotemporal dementia with inclusion body myopathy and Paget’s disease of bone IBMPFD is a rare autosomal dominant disorder caused by mutations in the gene valosincontaining protein VCP The CNS pathology is characterized by a novel pattern of ubiquitin pathology distinct from sporadic and familial frontotemporal lobar degeneration with ubiquitinpositive inclusions without VCP mutations Yet the ubiquitinpositive inclusions in IBMPFD also stain for TAR DNA binding protein a feature that links this rare disease with the pathology associated with the majority of sporadic FTD as well as disease resulting from different genetic alterations VCP a member of the AAAATPase gene family associates with a plethora of protein adaptors to perform a variety of cellular processes including Golgi assembly/disassembly and regulation of the ubiquitin–proteasome system However the mechanism whereby mutations in VCP lead to CNS muscle and bone disease is largely unknown In this report we review current literature on IBMPFD focusing on the pathology of the disease and the biology of VCP with respect to IBMPFD
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