Amyloid-β Inhibits PDGFβ Receptor Activation and Prevents PDGF-BB-Induced Neuroprotection

TitleAmyloid-β Inhibits PDGFβ Receptor Activation and Prevents PDGF-BB-Induced Neuroprotection
Publication TypeJournal Article
Year of Publication2018
AuthorsLiu, H., G. T. Saffi, M. S. Vasefi, Y. Choi, J. S. Kruk, N. Ahmed, N. Gondora, J. Mielke, Z. Leonenko, and M. A. Beazely
JournalCurrent Alzheimer Research
Volume15
Issue7
Pagination618-627
Date Published06/2018
KeywordsAlzheimer's disease, amyloid-beta, growth factor, neuroprotection, PDGF-BB, PDGFβ receptor
Abstract

BACKGROUND:

PDGFβ 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-β (1-42), one of the pathological agents associated with Alzheimer's disease (AD).

METHODS AND RESULTS:

In both primary hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y, amyloid-β treatment for 24 h decreased surviving cell number in a concentrationdependent manner. Pretreatment with PDGF-BB failed to provide any neuroprotection against amyloid-β 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-β attenuated the mitogenic effects of PDGF-BB, inhibited PDGF-BB-induced PDGFβ receptor phosphorylation, and attenuated the ability of PDGF-BB to protect neurons against NMDA-induced excitotoxicity. Despite the ability of amyloid-β to inhibit PDGFβ receptor activation, immunoprecipitation experiments failed to detect a physical interaction between amyloid-β and PDGF-BB or the PDGFβ receptor. However, G protein-coupled receptor transactivation of the PDGFβ receptor (an exclusively intracellular signaling pathway) remained unaffected by the presence of amyloid-β.

CONCLUSIONS:

As the PDGF system is upregulated upon neuronal damage, the ability of amyloid-β to inhibit this endogenous neuroprotective system should be further investigated in the context of AD pathophysiology.

URLhttp://www.eurekaselect.com/158917/article
DOI10.2174/1567205015666180110110321
Refereed DesignationRefereed