Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival.
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.
Van Damme
Philip
P
Laboratory of Neurobiology, Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Campus Gasthuisberg, 3000 Leuven, Belgium. philip.vandamme@med.kuleuven.be
Van Hoecke
Annelies
A
Lambrechts
Diether
D
Vanacker
Peter
P
Bogaert
Elke
E
van Swieten
John
J
Carmeliet
Peter
P
Van Den Bosch
Ludo
L
Robberecht
Wim
W
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
D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D000077153:Progranulins