MAPKS SIGNALING PATHWAYS REGULATES THE ACTIVATION OF LRP1 RECEPTOR ON THE INTERNALIZATION OF Aβ1-42 AND Aβ1-42-INDUCED NEUROTOXICITY

Abstract

Alzheimer's disease (AD) is one of common neurodegereation disease. The patients suffer from gradually memory loss. The pathological hallmarks of AD are the tau hyperphosphorylation induced neurofibrillary tangles (NFTs), the deposition of β-amyloid (Aβ) protein and a lot of neurons loss within the brain. Recently, it has been proposed that the intracelluar Aβ appears ealier than the extracellular Aβ. Cell cultured applied.The expression of proteins were assessed by Western blotting and immunoflurence. Biochemical tests were emploied.The quantitative analysis of intracellular Aβ was assayed with Elisa. Our immunoflurences results showed that the Aβ1-42 was internalized by SH-SY5Y cells. Aβ was colocalized with LRP1 in SH-SY5Y cells. The MAPKs (P38, JNK, ERK) were activated (P<0.05), the expression level of LRP1 (P<0.01) were also significantly increased, compared to the saline group, while the SH-SY5Y cells were treated with Aβ1-42. By using the p38 MAPK inhibitor SB202190, the expression of LRP1 level significantly decreased (P<0.05). ERK1/2 MAPK inhibitor decreases the level of LRP1 (P<0.01) expression. However, in JNK MAPK inhibitor treated group, the level of LRP1 (P<0.05) significantly increased. In the study of Aβ induced toxicity, Aβ (5 μM, 18 h) up-regulates the expression of Bcl2/Bax (P<0.05), and increases the Cyt c (P<0.01) release. The p38, ERK1/2 MAPK inhibitor could up-regulate the Bcl2/Bax (P<0.05) level, decrease the level of Cyt c (P<0.05) release. JNK MAPK inhibitor has no significant effects on the level of Bcl2/Bax and Cyt c. Exogenous Aβ could be internalized by SH-SY5Y cells; MAPK signaling pathways were activated by Aβ; The MAPK signaling pathways could regulate the Aβ level through the LRP1; Aβ was internalized and could induce toxic effect on SH-SY5Y cells.