Loss of progranulin function in frontotemporal lobar degeneration.
Frontotemporal lobar degeneration (FTLD) represents a collection of neurodegenerative diseases of frontal and temporal brain regions. It has long been associated with mutations in microtubule-associated protein tau (MAPT), and more recently with loss-of-function mutations in progranulin (PGRN). Phenotypes of PGRN and MAPT mutation carriers overlap, although disease onset in PGRN carriers is a decade later. Mutations in PGRN might influence susceptibility to a wider range of neurodegenerative diseases including Alzheimer and Parkinson diseases. The recent demonstration that mutations in PGRN result in FTLD provided a novel entrance point to the molecular mechanisms leading to this disorder. The high variability in onset age and age-dependent penetrance suggests that the PGRN pathway is highly susceptible to modulating factors that might be exploited to delay the disease processes.
Cruts
Marc
M
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
Van Broeckhoven
Christine
C
D000595:Amino Acid Sequence; D003704:Dementia / Q000235:genetics / Q000378:metabolism*; D004198:Disease Susceptibility; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D010641:Phenotype; D000077153:Progranulins
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins