Progranulin: An emerging target for FTLD therapies

Jennifer Gass, Mercedes Prudencio, Caroline Stetler, Leonard Petrucelli

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Frontotemporal lobar degeneration (FTLD), a neurodegenerative disease primarily affecting the frontal and temporal lobes, is one of the most common types of dementia. While the majority of FTLD cases are sporadic, approximately 10-40% of patients have an inherited form of FTLD. Mutations in the progranulin gene (GRN) have recently been identified as a major cause of FTLD with ubiquitin positive inclusions (FTLD-U). Because over 70 disease-linked GRN mutations cause abnormal deficiencies in the production of PGRN, a protein that plays a crucial role in embryogenesis, cell growth and survival, wound repair and inflammation, researchers now aim to design therapies that would increase PGRN levels in affected individuals, thereby alleviating the symptoms associated with disease. Several compounds and genetic factors, as well as PGRN receptors, have recently been identified because of their ability to regulate PGRN levels. Strict quality control measures are needed given that extreme PGRN levels at either end of the spectrum - too low or too high - can lead to neurodegeneration or cancer, respectively. The aim of this review is to highlight what is known regarding PGRN biology; to improve understanding of the mechanisms involved in regulating PGRN levels and highlight studies that are laying the groundwork for the development of effective therapeutic modulators of PGRN. This article is part of a Special Issue entitled RNA-Binding Proteins.

Original languageEnglish (US)
Pages (from-to)118-128
Number of pages11
JournalBrain Research
Volume1462
DOIs
StatePublished - Jun 26 2012

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Frontotemporal Lobar Degeneration
Frontotemporal Dementia
Mutation
Aptitude
RNA-Binding Proteins
Frontal Lobe
Temporal Lobe
Therapeutics
Neurodegenerative Diseases
Quality Control
Embryonic Development
Dementia
Cell Survival
Research Personnel
Inflammation
Wounds and Injuries
Growth
Genes
Neoplasms
Proteins

Keywords

  • Dementia
  • Frontotemporal lobar degeneration
  • Neurodegeneration
  • Neurotrophic factor
  • Progranulin
  • Sortilin

ASJC Scopus subject areas

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

Cite this

Progranulin : An emerging target for FTLD therapies. / Gass, Jennifer; Prudencio, Mercedes; Stetler, Caroline; Petrucelli, Leonard.

In: Brain Research, Vol. 1462, 26.06.2012, p. 118-128.

Research output: Contribution to journalArticle

Gass, Jennifer ; Prudencio, Mercedes ; Stetler, Caroline ; Petrucelli, Leonard. / Progranulin : An emerging target for FTLD therapies. In: Brain Research. 2012 ; Vol. 1462. pp. 118-128.
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