title: Inclusion body myopathy, Paget's disease of the bone and fronto-temporal dementia: a disorder of autophagy.
abstract: Inclusion body myopathy associated with Paget's disease of the bone and fronto-temporal dementia (IBMPFD) is a progressive autosomal dominant disorder caused by mutations in p97/VCP (valosin-containing protein). p97/VCP is a member of the AAA+ (ATPase associated with a variety of activities) protein family and participates in multiple cellular processes. One particularly important role for p97/VCP is facilitating intracellular protein degradation. p97/VCP has traditionally been thought to mediate the ubiquitin-proteasome degradation of proteins; however, recent studies challenge this dogma. p97/VCP clearly participates in the degradation of aggregate-prone proteins, a process principally mediated by autophagy. In addition, IBMPFD mutations in p97/VCP lead to accumulation of autophagic structures in patient and transgenic animal tissue. This is likely due to a defect in p97/VCP-mediated autophagosome maturation. The following review will discuss the evidence for p97/VCP in autophagy and how a disruption in this process contributes to IBMPFD pathogenesis.
authors.affiliation: Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Ju
authors.forename: Conrad C
authors.initials: CC
authors.lastname: Weihl
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000502:physiology; D001343:Autophagy; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D057180:Frontotemporal Dementia / Q000150:complications* / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000150:complications* / Q000235:genetics; D010001:Osteitis Deformans / Q000150:complications* / Q000235:genetics; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
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