title: Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival.
abstract: Recently, mutations in the progranulin (PGRN) gene were found to cause familial and apparently sporadic frontotemporal lobe dementia (FTLD). Moreover, missense changes in PGRN were identified in patients with motor neuron degeneration, a condition that is related to FTLD. Most mutations identified in patients with FTLD until now have been null mutations. However, it remains unknown whether PGRN protein levels are reduced in the central nervous system from such patients. The effects of PGRN on neurons also remain to be established. We report that PGRN levels are reduced in the cerebrospinal fluid from FTLD patients carrying a PGRN mutation. We observe that PGRN and GRN E (one of the proteolytic fragments of PGRN) promote neuronal survival and enhance neurite outgrowth in cultured neurons. These results demonstrate that PGRN/GRN is a neurotrophic factor with activities that may be involved in the development of the nervous system and in neurodegeneration.
authors: Laboratory of Neurobiology, Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Campus Gasthuisberg, 3000 Leuven, Belgium. philip.vandamme@med.kuleuven.be
authors: Philip
authors: P
authors: Van Damme
authors: Annelies
authors: A
authors: Van Hoecke
authors: Diether
authors: D
authors: Lambrechts
authors: Peter
authors: P
authors: Vanacker
authors: Elke
authors: E
authors: Bogaert
authors: John
authors: J
authors: van Swieten
authors: Peter
authors: P
authors: Carmeliet
authors: Ludo
authors: L
authors: Van Den Bosch
authors: Wim
authors: W
authors: Robberecht
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002470:Cell Survival; D003704:Dementia / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000166:cytology*; D000077153:Progranulins; D051381:Rats; D017208:Rats, Wistar
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D000077153:Progranulins