Losing protein in the brain: The case of progranulin

Roberta Ghidoni, Anna Paterlini, Valentina Albertini, Giuliano Binetti, Luisa Benussi

Research output: Contribution to journalArticlepeer-review

Abstract

It is well known that progranulin protein is involved in wound repair, inflammation, and tumor formation. The wedding between progranulin and brain was celebrated in 2006 with the involvement of progranulin gene (GRN) in Frontotemporal lobar degeneration (FTLD), the most common form of early-onset dementia: up to date, 75 mutations have been detected in FTLD patients as well as in patients with widely variable clinical phenotypes. All pathogenic GRN mutations identified thus far cause the disease through a uniform mechanism, i.e. loss of functional progranulin or haploinsufficiency. Studies on GRN knockout mice suggest that progranulin-related neurodegenerative diseases may result from lifetime depletion of neurotrophic support together with cumulative damage in association with dysregulated inflammation, thus highlighting possible new molecular targets for GRN-related FTLD treatment. Recently, the dosage of plasma progranulin has been proposed as a useful tool for a quick and inexpensive large-scale screening of affected and unaffected carriers of GRN mutations. Before it is systematically translated into clinical practice and, more importantly, included into diagnostic criteria for dementias, further standardization of plasma progranulin test and harmonization of its use are required. Once a specific treatment becomes available for these pathologies, this test - being applicable on large scale - will represent an important step towards personalized healthcare. This article is part of a Special Issue entitled: Brain Integration.

Original languageEnglish
Pages (from-to)172-182
Number of pages11
JournalBrain Research
Volume1476
DOIs
Publication statusPublished - Oct 2 2012

Keywords

  • Clinical phenotype
  • Frontotemporal lobar degeneration
  • Haploinsufficiency
  • Neurodegeneration
  • Plasma progranulin cutoff
  • Progranulin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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