Ahmed Zeshan, Mackenzie Ian R A, Hutton Michael L, Dickson Dennis W
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA.
J Neuroinflammation. 2007 Feb 11;4:7. doi: 10.1186/1742-2094-4-7.
Progranulin (PGRN) is a pleiotropic protein that has gained the attention of the neuroscience community with recent discoveries of mutations in the gene for PGRN that cause frontotemporal lobar degeneration (FTLD). Pathogenic mutations in PGRN result in null alleles, and the disease is likely the result of haploinsufficiency. Little is known about the normal function of PGRN in the central nervous system apart from a role in brain development. It is expressed by microglia and neurons. In the periphery, PGRN is involved in wound repair and inflammation. High PGRN expression has been associated with more aggressive growth of various tumors. The properties of full length PGRN are distinct from those of proteolytically derived peptides, referred to as granulins (GRNs). While PGRN has trophic properties, GRNs are more akin to inflammatory mediators such as cytokines. Loss of the neurotrophic properties of PGRN may play a role in selective neuronal degeneration in FTLD, but neuroinflammation may also be important. Gene expression studies suggest that PGRN is up-regulated in a variety of neuroinflammatory conditions, and increased PGRN expression by microglia may play a pivotal role in the response to brain injury, neuroinflammation and neurodegeneration.
颗粒蛋白前体（PGRN）是一种多效性蛋白，随着最近发现导致额颞叶痴呆（FTLD）的PGRN基因突变，它已引起神经科学界的关注。PGRN中的致病突变会导致无效等位基因，而该疾病可能是单倍剂量不足的结果。除了在大脑发育中的作用外，人们对PGRN在中枢神经系统中的正常功能知之甚少。它由小胶质细胞和神经元表达。在周围组织中，PGRN参与伤口修复和炎症反应。高PGRN表达与各种肿瘤的侵袭性生长有关。全长PGRN的特性与蛋白水解衍生肽（称为颗粒蛋白（GRNs））的特性不同。虽然PGRN具有营养特性，但GRNs更类似于细胞因子等炎症介质。PGRN营养特性的丧失可能在FTLD的选择性神经元变性中起作用，但神经炎症也可能很重要。基因表达研究表明，PGRN在多种神经炎症条件下上调，小胶质细胞中PGRN表达的增加可能在对脑损伤、神经炎症和神经变性的反应中起关键作用。
