Plasma rich in growth factors (PRGF-Endoret) reduces neuropathologic hallmarks and improves cognitive functions in an Alzheimer's disease mouse model

被引:43
作者
Anitua, Eduardo [1 ]
Pascual, Consuelo [2 ,3 ]
Antequera, Desiree [2 ,3 ]
Bolos, Marta [2 ,3 ]
Padilla, Sabino [1 ]
Orive, Gorka [1 ]
Carro, Eva [2 ,3 ]
机构
[1] Fdn Eduardo Anitua, Vitoria 01007, Alava, Spain
[2] Hosp 12 Octubre I 12, Inst Invest, Neurosci Grp, Madrid, Spain
[3] Biomed Res Networking Ctr Neurodegenerat Dis CIBE, Madrid, Spain
关键词
Alzheimer's disease; PRGF-Endoret; Intranasal administration; A beta degradation; Cognition; Astrocytes; Transgenic mice; Cognitive impairment; AMYLOID PRECURSOR PROTEIN; DYSTROPHIC NEURITES; TRANSGENIC MOUSE; MEMORY DEFICITS; FACTOR-I; BETA; INFLAMMATION; PATHOLOGY; ASTROCYTES; INSULIN;
D O I
10.1016/j.neurobiolaging.2014.01.009
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Impaired growth factor function is thought to drive many of the alterations observed in Alzheimer's disease (AD) patients. Endogenous regenerative technology, PRGF (plasma rich in growth factor)-Endoret, is designed for the delivery of a complex pool of patient's own active morphogens that may stimulate tissue regeneration. We obtained and characterized PRGF-Endoret preparations from human blood. We used, as experimental approach in vivo, APP/PS1 mice, characterized by age-dependent brain amyloid-beta (A beta) accumulation. Intranasal administration of PRGF-Endoret to APP/PS1 mice resulted in an important decrease in brain A beta deposition and tau phosphorylation. PRGF-Endoret-treated APP/PS1 mice also showed decreased astrocyte reactivity, and prevented protein synaptic loss. In vitro approaches demonstrated that PRGF-Endoret treatment modulated astrocyte activation, reducing inflammatory responses, and promoted A beta degradation. Furthermore, PRGF-Endoret stimulated global improvements in anxiety, learning, and memory behaviors. Our findings show that PRGF-Endoret exerts multifunctional and complementary effects that result in the reversal of the broad range of cognitive deficits in AD, suggesting that PRGF-Endoret may hold promise as an innovative therapy in AD. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:1582 / 1595
页数:14
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