Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process

Frontiers in Molecular Neuroscience

Yu Yamazaki¹  Masahiro Nakamori¹  Keyoumu Nazere¹  Kazuki Muguruma¹  Hirofumi Maruyama¹  Naoyuki Hara¹  Hiroyuki Morino²  Tetsuya Takahashi³ 

[1] Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan;Department of Medical Genetics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan;Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan;

关键词: Alzheimer’s disease;    amyloid – beta;    HSPG;    lipid raft;    macropinocytosis;    Rac1;   

DOI  :  10.3389/fnmol.2022.804702

来源: DOAJ

【 摘 要 】

Intracellular amyloid β peptide (Aβ) accumulation has drawn attention in relation to the pathophysiology of Alzheimer’s disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aβ is one of the possible mechanisms by which intracellular Aβ deposits form. Given the relevance of Aβ inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aβ in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-β-cyclodextrin or treatment with trypsin diminished the internalization of oAβ, suggesting that the oAβ uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aβ (oAβ). oAβ-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAβ is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAβ42 enters cells.

【 授权许可】

Unknown