Autophagy is involved in oligodendroglial precursor-mediated clearance of amyloid peptide.
BACKGROUND
Accumulation of β-amyloid peptides is an important hallmark of Alzheimer's disease (AD). Tremendous efforts have been directed to elucidate the mechanisms of β-amyloid peptides degradation and develop strategies to remove β-amyloid accumulation. In this study, we demonstrated that a subpopulation of oligodendroglial precursor cells, also called NG2 cells, were a new cell type that can clear β-amyloid peptides in the AD transgene mice and in NG2 cell line.


RESULTS
NG2 cells were recruited and clustered around the amyloid plaque in the APPswe/PS1dE9 mice, which is Alzheimer's disease mouse model. In vitro, NG2 cell line and primary NG2 cells engulfed β-amyloid peptides through the mechanisms of endocytosis in a time dependent manner. Endocytosis is divided into pinocytosis and phagocytosis. Aβ(42) internalization by NG2 cells was mediated by actin-dependent macropinocytosis. The presence of β-amyloid peptides stimulated the autophagic pathway in NG2 cells. Once inside the cells, the β-amyloid peptides in NG2 cells were transported to lysosomes and degraded by autophagy.


CONCLUSIONS
Our findings suggest that NG2 cells are a new cell type that can clear β-amyloid peptides through endocytosis and autophagy.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
Wenxia
W
Li
Yifen
Y
Tang
Zhiqin
Z
Fan
Ya
Y
Meng
Guang
G
Yang
Jia
J
Luo
Zun-Ji
ZJ
Ke
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D058953:Neural Stem Cells / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
D016229:Amyloid beta-Peptides; D034741:RNA, Small Interfering