• 作者：Jinlong Jian^a ; Shuai Zhao^a ; Qing-Yun Tian^a ; Helen Liu^a ; Yunpeng Zhao^a ; Wen-Chi Chen^b ; Gabriele Grunig^b ; Paola A. Torres^c ; Betty C. Wang^c ; Bai Zeng^c ; Gregory Pastores^c ; Wei Tang^d ; Ying Sun^e ; Gregory A. Grabowski^e ; Max Xiangtian Kong^f ; Guilin Wang^g ; Ying Chen^h ; Fengxia Liangⁱ ; Herman S. Overkleeft^j ; Rachel Saunders-Pullman^k ; Gerald L. Chan^l ; Chuan-ju Liu^a ; ^m ; ^{chuanju.liu@nyumc.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Progranulin ; β-Glucocerebrosidase ; Gaucher disease ; Lysosomal storage diseases
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：11
• 期：Complete
• 页码：127-137
• 全文大小：2956 K

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The serum levels of PGRN is significantly lower in Gaucher's disease patients.

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4 GRN gene SNPs exhibit significantly higher frequencies in Gaucher's disease patients.

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Both OVA-challenged and aged PGRN deficient mice develop Gaucher-like disease.

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PGRN deficiency causes GCase aggregation and absence in lysosomes.

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rPGRN protein is therapeutic against Gaucher's disease.

The present study revealed 1) PGRN was isolated as an unexpected molecule associated with GD in addition to GCase; 2) deficiency or insufficiency of PGRN contributes to Gaucher's disease in mice and humans; 3) PGRN is required for the lysosomal localization of GCase; 4) measuring serum levels of PGRN and detecting variants in GRN may be employed as biochemical and genetic diagnostic approaches for GD; 5) novel therapeutic utilities for treating GD may implement PGRN in addition to recombinant GCase; and 6) this study also presents an unique mouse model that mimics the cardinal signs of human GD, including the typical tubular-like lysosomes in macrophages always seen in human GD patients, but not observed in any GD animal models previously reported.