期刊
NEUROBIOLOGY OF AGING
卷 35, 期 7, 页码 1582-1595出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.01.009
关键词
Alzheimer's disease; PRGF-Endoret; Intranasal administration; A beta degradation; Cognition; Astrocytes; Transgenic mice; Cognitive impairment
资金
- Foundation Eduardo Anitua
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.
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