title: Frontotemporal lobar degeneration with ubiquitin-positive inclusions: a molecular genetic update.
abstract: Frontotemporal lobar degeneration (FTLD) is a clinically, pathologically and genetically highly complex disorder. In the last few years enormous progress has been made in dissecting the genetic etiology of FTLD. Mutations have been identified in the progranulin gene (PGRN), the charged multivesicular body protein 2B gene (CHMP2B) and the valosin-containing protein gene (VCP). Mutations in these genes all lead to FTLD pathology characterized by ubiquitin-immunoreactive neuronal cytoplasmic and intranuclear lentiform inclusions (FTLD-U). The similar pathology suggests that these genes may be connected trough a common disease pathway leading to neurodegeneration and the formation of these pathognomic inclusions. This review focuses on the molecular genetic processes underlying FTLD-U pathology.
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Laboratory of Neurogenetics, Institute Born-Bunge, and University of Antwerp, Antwerp, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: van der Zee
authors.forename: Ilse
authors.initials: I
authors.lastname: Gijselinck
authors.forename: Daniel
authors.initials: D
authors.lastname: Pirici
authors.forename: Samir
authors.initials: S
authors.lastname: Kumar-Singh
authors.forename: Marc
authors.initials: M
authors.lastname: Cruts
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D003704:Dementia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D000077153:Progranulins; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D000074405:Valosin Containing Protein
chemical_list: C503812:CHMP2B protein, human; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000077153:Progranulins; D025801:Ubiquitin; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein