Human genetics as a tool to identify progranulin regulators

Alexandra M. Nicholson, Nicole A. Finch, Rosa Rademakers

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Frontotemporal lobar degeneration (FTLD) is a common neurodegenerative disorder that predominantly affects individuals under the age of 65. It is known that the most common pathological subtype is FTLD with TAR DNA-binding protein 43 inclusions (FTLD-TDP). FTLD has a strong genetic component with about 50% of cases having a positive family history. Mutations identified in the progranulin gene (GRN) have been shown to cause FTLD-TDP as a result of progranulin haploinsufficiency. These findings suggest a progranulin-dependent mechanism in this pathological FTLD subtype. Thus, identifying regulators of progranulin levels is essential for new therapies and treatments for FTLD and related disorders. In this review, we discuss the role of genetic studies in identifying progranulin regulators, beginning with the discovery of pathogenic GRN mutations and additional GRN risk variants. We also cover more recent genetic advances, including the detection of variants in the transmembrane protein 106 B gene that increase FTLD-TDP risk presumably by modulating progranulin levels and the identification of a potential progranulin receptor, sortilin. This review highlights the importance of genetic studies in the context of FTLD and further emphasizes the need for future genetic and cell biology research to continue the effort in finding a cure for progranulin-related diseases.

Original languageEnglish (US)
Pages (from-to)532-537
Number of pages6
JournalJournal of Molecular Neuroscience
Volume45
Issue number3
DOIs
StatePublished - Nov 2011

Keywords

  • FTLD
  • Genetics
  • Progranulin
  • Sortilin
  • TDP-43
  • TMEM106B

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Human genetics as a tool to identify progranulin regulators'. Together they form a unique fingerprint.

Cite this