title: Plasma rich in growth factors (PRGF-Endoret) reduces neuropathologic hallmarks and improves cognitive functions in an Alzheimer's disease mouse model.
abstract: 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-β (Aβ) accumulation. Intranasal administration of PRGF-Endoret to APP/PS1 mice resulted in an important decrease in brain Aβ 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 Aβ 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.
authors: Foundation Eduardo Anitua, Vitoria, Spain.
authors: Eduardo
authors: E
authors: Anitua
authors: Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors: Consuelo
authors: C
authors: Pascual
authors: Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors: Desiree
authors: D
authors: Antequera
authors: Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors: Marta
authors: M
authors: Bolos
authors: Foundation Eduardo Anitua, Vitoria, Spain.
authors: Sabino
authors: S
authors: Padilla
authors: Foundation Eduardo Anitua, Vitoria, Spain. Electronic address: gorka.orive@fundacioneduardoanitua.org.
authors: Gorka
authors: G
authors: Orive
authors: Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain. Electronic address: carroeva@h12o.es.
authors: Eva
authors: E
authors: Carro
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001007:Anxiety; D001253:Astrocytes / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000494:pharmacology / Q000502:physiology; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000187:drug effects; D010949:Plasma; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D036341:Intercellular Signaling Peptides and Proteins; D016875:tau Proteins
keywords: Alzheimer's disease; Astrocytes; Aβ degradation; Cognition; Cognitive impairment; Intranasal administration; PRGF-Endoret; Transgenic mice