Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival

被引：344

作者：

Van Damme, Philip ^{[1
,2
,3
]}

Van Hoecke, Annelies ^{[1
,3
]}

Lambrechts, Diether ^{[3
,4
]}

Vanacker, Peter ^{[1
,2
]}

Bogaert, Elke ^{[1
,3
]}

Van Swieten, John ^{[5
]}

Carmeliet, Peter ^{[3
,4
]}

Van den Bosch, Ludo ^{[1
,3
]}

Robberecht, Wim ^{[1
,2
,3
]}

机构：

[1] Katholieke Univ Leuven, Neurobiol Lab, B-3000 Louvain, Belgium

[2] Katholieke Univ Leuven, Dept Neurol, B-3000 Louvain, Belgium

[3] Katholieke Univ Leuven, Dept Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium

[4] Katholieke Univ Leuven, Katholieke Univ Leuven VIB, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium

[5] Erasmus MC Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands

来源：

JOURNAL OF CELL BIOLOGY | 2008年 / 181卷 / 01期

关键词：

D O I：

10.1083/jcb.200712039

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：37 / 41

页数：5

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