Abstract:

Objective To investigate the neuroprotection effect of transferrin receptor 1(TfR1) in Alzheimer’s disease(AD). Methods Immunofluorescence and Western blotting were used to detect the expression of TfR1 in the amyloid precursor protein（APP）/presenilin-1（PS1）transgenic mice from postnatal 0 day(P0) to P360. With primary cultured hippocampal neurons, TfR1 expression and amyloid betapeptides (Aβ) secretion were detected with Western blotting and ELISA assay, respectively. The cultured neurons and their processes were labeled with TfR1 and microtubule associated protein 2 (MAP2) immunolabeling, and the TfR1-mediated axonal vesicles were observed with FM1-43 staining, after TfR1 shRNA interference. Results TfR1 expression in AD mice (APP/PS1 transgenic mice) decreased significantly after postnatal 6 months (P 6 M) compared with the wild type(WT) mice. Similarly, in cultured cells, after TfR1 gene silence, the neuronal processes became long and thin, and the axonal vesicle transportation was blocked. Conclusion APP and PS1 gene mutation can decrease expression of TfR1. TfR1 shRNA interference can increase the amount of Aβ_1-42 secretion and impact neurite growth and axonal vesicle transportation. Therefore, we conclude that TfR1 may play an important role in neuroprotection.

Key words: Transferrin receptor 1, Transfection, Interference, Primary neuron, Vesicular transport, Dendrite, Western blotting, Mouse