Preclinical Interventions in Mouse Models of Frontotemporal Dementia Due to Progranulin Mutations.
Preclinical Interventions in Mouse Models of Frontotemporal Dementia Due to Progranulin Mutations.
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DOI：
10.1007/s13311-023-01348-6
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发表时间：
2023-01
影响因子：
5.7
通讯作者：
Roberson, Erik D.
中科院分区：
文献类型：
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作者：
Kashyap, Shreya N.;Boyle, Nicholas R.;Roberson, Erik D.
颗粒蛋白前体（GRN）的杂合功能丧失突变导致额颞叶痴呆（FTD），这是早发性痴呆的主要原因，临床特征为行为、社交和语言缺陷。目前还没有FDA批准的FTD-GRN治疗方法，但这一直是一个活跃的研究领域，目前有几种方法正在进行临床试验。在这里，我们回顾了FTD-GRN疗法的临床前开发，重点是在小鼠模型中进行测试。由于大多数FTD-GRN相关突变导致颗粒蛋白前体单倍不足，这些方法专注于提高颗粒蛋白前体水平。我们开始考虑与改变颗粒蛋白前体水平的疾病，然后审查颗粒蛋白前体生物学的基础知识，包括其溶酶体，神经营养和免疫调节功能。我们讨论了小鼠模型的颗粒蛋白前体不足，以及它们如何被用于临床前研究的各种治疗方法。这些方法包括提高正常等位基因的颗粒蛋白前体表达或促进突变等位基因的颗粒蛋白前体产生的方法，以及通过穿过血脑屏障递送或通过基因治疗直接增加颗粒蛋白前体水平的方法。其中一些方法已经进入临床试验，为FTD-GRN的新疗法可能成为治疗神经退行性疾病的下一个前沿提供了希望。在线版本包含补充材料，可通过10.1007/s13311-023-01348-6获得。
Heterozygous loss-of-function mutations in progranulin (GRN) cause frontotemporal dementia (FTD), a leading cause of early-onset dementia characterized clinically by behavioral, social, and language deficits. There are currently no FDA-approved therapeutics for FTD-GRN, but this has been an active area of investigation, and several approaches are now in clinical trials. Here, we review preclinical development of therapies for FTD-GRN with a focus on testing in mouse models. Since most FTD-GRN-associated mutations cause progranulin haploinsufficiency, these approaches focus on raising progranulin levels. We begin by considering the disorders associated with altered progranulin levels, and then review the basics of progranulin biology including its lysosomal, neurotrophic, and immunomodulatory functions. We discuss mouse models of progranulin insufficiency and how they have been used in preclinical studies on a variety of therapeutic approaches. These include approaches to raise progranulin expression from the normal allele or facilitate progranulin production by the mutant allele, as well as approaches to directly increase progranulin levels by delivery across the blood–brain barrier or by gene therapy. Several of these approaches have entered clinical trials, providing hope that new therapies for FTD-GRN may be the next frontier in the treatment of neurodegenerative disease. The online version contains supplementary material available at 10.1007/s13311-023-01348-6.
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影响因子：
3.7
作者：
Dobson-Stone C;Hallupp M;Loy CT;Thompson EM;Haan E;Sue CM;Panegyres PK;Razquin C;Seijo-Martínez M;Rene R;Gascon J;Campdelacreu J;Schmoll B;Volk AE;Brooks WS;Schofield PR;Pastor P;Kwok JB
通讯作者：
Kwok JB
Fabry病的酶替代疗法：系统评价和荟萃分析。
影响因子：
2.1
作者：
Alegra T;Vairo F;de Souza MV;Krug BC;Schwartz IV
通讯作者：
Schwartz IV
影响因子：
8.8
作者：
Almeida S;Zhang Z;Coppola G;Mao W;Futai K;Karydas A;Geschwind MD;Tartaglia MC;Gao F;Gianni D;Sena-Esteves M;Geschwind DH;Miller BL;Farese RV Jr;Gao FB
通讯作者：
Gao FB
影响因子：
3.5
作者：
Beel S;Moisse M;Damme M;De Muynck L;Robberecht W;Van Den Bosch L;Saftig P;Van Damme P
通讯作者：
Van Damme P
DOI：
10.1007/s12032-017-1054-7
发表时间：
2017-11-07
期刊：
Medical oncology (Northwood, London, England)
影响因子：
--
作者：
Arechavaleta-Velasco F;Perez-Juarez CE;Gerton GL;Diaz-Cueto L
通讯作者：
Diaz-Cueto L