Circulating progranulin as a biomarker for neurodegenerative diseases

Research output: Contribution to journalReview article

Abstract

Progranulin is a growth factor involved in the regulation of multiple processes including tumorigenesis, wound repair, development, and inflammation. The recent discovery that mutations in the gene encoding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD), and other neurodegenerative diseases leading to dementia, has brought renewed interest in progranulin and its functions in the central nervous system. GRN null mutations cause protein haploinsufficiency, leading to a significant decrease in progranulin levels that can be detected in plasma, serum and cerebrospinal fluid (CSF) of mutation carriers. The dosage of circulating progranulin sped up the identification of GRN mutations thus favoring genotype-phenotype correlation studies. Researchers demonstrated that, in GRN null mutation carriers, the shortage of progranulin invariably precedes clinical symptoms and thus mutation carriers are “captured” regardless of their disease status. GRN is a particularly appealing gene for drug targeting, in the way that boosting its expression may be beneficial for mutation carriers, preventing or delaying the onset of GRN-related neurodegenerative diseases. Physiological regulation of progranulin expression level is only partially known. Progranulin expression reflects mutation status and, intriguingly, its levels can be modulated by some additional factor (i.e. genetic background; drugs). Thus, factors increasing the production and secretion of progranulin from the normal gene are promising potential therapeutic avenues. In conclusion, peripheral progranulin is a nonintrusive highly accurate biomarker for early identification of mutation carriers and for monitoring future treatments that might boost the level of this protein.

Original languageEnglish
Pages (from-to)180-190
Number of pages11
JournalAmerican Journal of Neurodegenerative Diseases
Volume1
Issue number2
Publication statusPublished - Aug 15 2012

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Keywords

  • Blood
  • CSF
  • Cut-off
  • Dementia
  • Expression
  • Frontotemporal
  • GRN
  • Haploinsufficiency
  • Modulator
  • Progranulin

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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