Amyloid-ß Inhibits PDGFß Receptor Activation and Prevents PDGF-BBInduced Neuroprotection.
Curr Alzheimer Res
; 15(7): 618-627, 2018.
Article
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| MEDLINE
| ID: mdl-29332578
ABSTRACT
BACKGROUND:
PDGFß receptors and their ligand, PDGF-BB, are upregulated in vivo after neuronal insults such as ischemia. When applied exogenously, PDGF-BB is neuroprotective against excitotoxicity and HIV proteins.OBJECTIVE:
Given this growth factor's neuroprotective ability, we sought to determine if PDGF-BB would be neuroprotective against amyloid-ß (1-42), one of the pathological agents associated with Alzheimer's disease (AD). METHODS ANDRESULTS:
In both primary hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y, amyloid-ß treatment for 24 h decreased surviving cell number in a concentrationdependent manner. Pretreatment with PDGF-BB failed to provide any neuroprotection against amyloid-ß in primary neurons and only very limited protective effects in SH-SY5Y cells. In addition to its neuroprotective action, PDGF promotes cell growth and division in several systems, and the application of PDGFBB alone to serum-starved SH-SY5Y cells resulted in an increase in cell number. Amyloid-ß attenuated the mitogenic effects of PDGF-BB, inhibited PDGF-BB-induced PDGFß receptor phosphorylation, and attenuated the ability of PDGF-BB to protect neurons against NMDA-induced excitotoxicity. Despite the ability of amyloid-ß to inhibit PDGFß receptor activation, immunoprecipitation experiments failed to detect a physical interaction between amyloid-ß and PDGF-BB or the PDGFß receptor. However, G protein-coupled receptor transactivation of the PDGFß receptor (an exclusively intracellular signaling pathway) remained unaffected by the presence of amyloid-ß.CONCLUSIONS:
As the PDGF system is upregulated upon neuronal damage, the ability of amyloid-ß to inhibit this endogenous neuroprotective system should be further investigated in the context of AD pathophysiology.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Fármacos Neuroprotectores
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Receptor beta de Factor de Crecimiento Derivado de Plaquetas
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Becaplermina
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Hipocampo
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Neuronas
Límite:
Animals
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Humans
Idioma:
En
Revista:
Curr Alzheimer Res
Asunto de la revista:
NEUROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Canadá