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Valosin containing protein associated fronto-temporal lobar degeneration: clinical presentation, pathologic features

C C Weihl1

  • 1Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA. weihlc@neuro.wustl.edu

Current Alzheimer Research
|January 13, 2011
PubMed

Insights

Inclusion body myopathy, Paget's disease, and frontotemporal dementia (IBMPFD) result from VCP gene mutations disrupting protein degradation. This review focuses on the central nervous system degeneration seen in IBMPFD.

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Inclusion body myopathy, Paget's disease of the bone, and frontotemporal dementia (IBMPFD) is a rare multisystem disorder.
  • Mutations in the valosin-containing protein (VCP) gene cause IBMPFD.
  • VCP protein is crucial for protein degradation via ubiquitin-proteasome and autophagy pathways.

Purpose of the Study:

  • To review the clinical and pathological features of IBMPFD, focusing on central nervous system degeneration.
  • To explore the role of VCP in terminally differentiated tissues.
  • To understand how VCP mutations lead to myo- and neurodegeneration.

Main Methods:

  • Literature review of IBMPFD, VCP function, and related pathologies.
  • Analysis of ubiquitinated and TDP-43 inclusions in affected tissues.
  • Discussion of VCP's role in protein homeostasis.

Main Results:

  • IBMPFD is characterized by ubiquitinated and TDP-43 inclusions in brain and muscle.
  • VCP mutations impair its protein degradation functions.
  • Pathology in skeletal muscle aligns with inclusion body myopathy (IBM).
  • Central nervous system pathology represents a frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) subtype.

Conclusions:

  • VCP mutations disrupt protein degradation, leading to IBMPFD.
  • Understanding VCP's function is key to addressing the neurodegenerative aspects of IBMPFD.
  • Further research into VCP's role in terminally differentiated cells may reveal therapeutic targets.

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