title: Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy.
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 valosin-containing protein (VCP). The CNS pathology is characterized by a novel pattern of ubiquitin pathology distinct from sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive inclusions without VCP mutations. Yet, the ubiquitin-positive 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 AAA-ATPase 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.
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Blvd., 605B Stellar-Chance Building, Philadelphia, PA, 19104-6140, USA.
authors: Jake B
authors: JB
authors: Guinto
authors: Gillian P
authors: GP
authors: Ritson
authors: J Paul
authors: JP
authors: Taylor
authors: Mark S
authors: MS
authors: Forman
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D003704:Dementia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D018979:Myositis, Inclusion Body / Q000150:complications / Q000235:genetics / Q000473:pathology; D010001:Osteitis Deformans / Q000150:complications / Q000235:genetics / Q000473:pathology; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein