Jennifer Gass and Leonard Petrucelli

in Amyotrophic Lateral Sclerosis and the Frontotemporal Dementias

Published on behalf of Oxford University Press

Published in print October 2012 | ISBN: 9780199590674
Published online November 2012 | e-ISBN: 9780191753466 | DOI:

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Progranulin (PGRN), a widely secreted growth factor, plays a role in the pathogenesis of multiple diseases, but new studies showing a link between a loss of PGRN and neurodegeneration have encouraged scientists searching for treatments. PGRN is involved in multiple biological functions, including cell growth and survival, embryogenesis, wound repair, and inflammation. Recent genetic evidence identified pathogenic mutations located within GRN as a major cause of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FLTD-U). These mutations, mostly non-sense, create a haploinsufficiency generating a loss of PGRN in these patients.

Currently, the role of PGRN in the central nervous system (CNS) remains relatively unknown; however, ongoing research in this area is furthering understanding. In humans, 6 kDa granulin repeats are derived from the precursor protein PGRN, which is also known as granulin–epithelin precursor, proepithelin, PC cell derived growth factor, and acrogranin.

While elevated levels of PGRN have been associated with various types of cancer, the loss of PGRN caused by mutations is linked to neurodegeneration. Determining how variations in the level of PGRN affect biological function is pertinent to potential treatment methods for FTLD-U and cancer. This chapter will highlight the functional and biochemical roles of PGRN, and how a decrease in PGRN neurotrophic support may lead to increased risk of cell death and neurodegenerative disease.

Chapter.  6389 words.  Illustrated.

Subjects: Neurology

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