Journal
FRONTIERS IN MOLECULAR NEUROSCIENCE
Volume 15, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2022.804702
Keywords
Alzheimer's disease; amyloid; beta; HSPG; lipid raft; macropinocytosis; Rac1
Categories
Funding
- Grant-in-Aid for Scientific Research [JP19K07974]
- Ministry of Education, Culture, Sports, Science and Technology
Ask authors/readers for more resources
Intracellular accumulation of oligomerized Aβ is mediated by lipid raft and heparan sulfate proteoglycan, while macropinocytosis is the major endocytic pathway for oligomer-Aβ entry into cells.
Intracellular amyloid beta peptide (A beta) 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 A beta is one of the possible mechanisms by which intracellular A beta deposits form. Given the relevance of A beta 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 A beta in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-beta-cyclodextrin or treatment with trypsin diminished the internalization of oA beta, suggesting that the oA beta 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-A beta (oA beta). oA beta-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oA beta is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oA beta 42 enters cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available