Inclusion body myopathy, Paget's disease of the bone and fronto-temporal dementia: A disorder of autophagy

Jeong Sun Ju, Conrad C. Weihl

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

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 AAA1 (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.

Original languageEnglish
Article numberddq157
Pages (from-to)R38-R45
JournalHuman molecular genetics
Volume19
Issue numberR1
DOIs
StatePublished - Apr 21 2010

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