Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Children's and Women's Hospital, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4.
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Children's and Women's Hospital, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4; Division of Neurology, Department of Medicine, University of British Columbia Hospital, S 192, 2211 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5; Brain Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Trends Neurosci. 2014 Jul;37(7):388-98. doi: 10.1016/j.tins.2014.04.003. Epub 2014 May 4.
Loss-of-function mutations in the progranulin gene are a common cause of familial frontotemporal dementia (FTD). The purpose of this review is to summarize the role of progranulin in health and disease, because the field is now poised to begin examining therapeutics that alter endogenous progranulin levels. We first review the clinical and neuropathological phenotype of FTD patients carrying mutations in the progranulin gene, which suggests that progranulin-mediated neurodegeneration is multifactorial and influenced by other genetic and/or environmental factors. We then examine evidence for the role of progranulin in the brain with a focus on mouse model systems. A better understanding of the complexity of progranulin biology in the brain will help guide the development of progranulin-modulating therapies for neurodegenerative disease.
颗粒蛋白前体基因的功能丧失性突变是家族性额颞叶痴呆（FTD）的常见病因。本篇综述旨在总结颗粒蛋白前体在健康和疾病中的作用，因为目前该领域正准备开始研究改变内源性颗粒蛋白前体水平的治疗方法。我们首先综述了携带颗粒蛋白前体基因突变的 FTD 患者的临床和神经病理学表型，这表明颗粒蛋白前体介导的神经退行性变是多因素的，并受其他遗传和/或环境因素的影响。然后，我们检查了颗粒蛋白前体在大脑中的作用证据，重点是小鼠模型系统。深入了解颗粒蛋白前体在大脑中的复杂性将有助于指导针对神经退行性疾病的颗粒蛋白调节治疗的发展。
