Atg5 deficit exaggerates the lysosome formation and cathepsin B activation in mice brain after lipid nanoparticles injection.
The present study was designed to investigate the role of autophagy-lysosome signaling in the brain after application of nanoparticles. Here, lipid nanoparticles (LNs) induced elevations of Atg5, P62, LC3 and cathepsin B in mice brain. The transmission electron microscopy revealed a dramatic elevation of lysosome vacuoles colocalized with LNs cluster inside the neurons in mice brain. Immunoblot data revealed abnormal expression of cathepsin B in brain cortex following LNs injection, whereas its expression was further elevated in Atg5(+/-) mice. The importance of Atg5 in the LNs-induced autophagy-lysosome cascade was further supported by our finding that neurovascular response was exaggerated in Atg5(+/-) mice. In addition, the siRNA knockdown of Atg5 significantly blunted the increasing of LC3 and P62 in LNs-treated Neuro-2a cells. Taken together, we propose that LNs induce autophagy-lysosome signaling and neurovascular response at least partially via an Atg5-dependent pathway.


BACKGROUND
These authors investigated autophagy-lysosome signaling in the mouse brain after application of lipid nanoparticles and report that these nanoparticles induce autophagy-lysosome signaling and neurovascular response at least partially via an Atg5-dependent pathway.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Nan-nan
NN
Lu
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Jun
J
Liu
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Yun
Y
Tian
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Mei-hua
MH
Liao
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Huan
H
Wang
School of Medicine, Zhejiang University City College, Hangzhou, China.
Ying-mei
YM
Lu
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Rong-rong
RR
Tao
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Ling-Juan
LJ
Hong
The Imaging Center, Core Facilities of Zhejiang University School of Medicine, Hangzhou, China.
Shuang-shuang
SS
Liu
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan.
Kohji
K
Fukunaga
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Yong-zhong
YZ
Du
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. Electronic address: changhuahan@zju.edu.cn.
Feng
F
Han
D000818:Animals; D000071187:Autophagy-Related Protein 5; D001921:Brain / Q000378:metabolism*; D002401:Cathepsin B / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics; D053758:Nanoparticles / Q000737:chemistry*
C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008055:Lipids; D008869:Microtubule-Associated Proteins; D002401:Cathepsin B
Atg5; Autophagy; Brain; Lipid nanoparticles; Neurovascular damage