Geniposide Alleviates Amyloid-Induced Synaptic Injury by Protecting Axonal Mitochondrial Trafficking.
Synaptic and mitochondrial pathologies are early events in the progression of Alzheimer's disease (AD). Normal axonal mitochondrial function and transport play crucial roles in maintaining synaptic function by producing high levels of adenosine triphosphate and buffering calcium. However, there can be abnormal axonal mitochondrial trafficking, distribution, and fragmentation, which are strongly correlated with amyloid-β (Aβ)-induced synaptic loss and dysfunction. The present study examined the neuroprotective effect of geniposide, a compound extracted from gardenia fruit in Aβ-treated neurons and an AD mouse model. Geniposide alleviated Aβ-induced axonal mitochondrial abnormalities by increasing axonal mitochondrial density and length and improving mitochondrial motility and trafficking in cultured hippocampal neurons, consequently ameliorating synaptic damage by reversing synaptic loss, addressing spine density and morphology abnormalities, and ameliorating the decreases in synapse-related proteins in neurons and APPswe/PS1dE9 mice. These findings provide new insights into the effects of geniposide administration on neuronal and synaptic functions under conditions of Aβ enrichment.
Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal UniversityBeijing, China; College of Life Science, Beijing Normal UniversityBeijing, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal UniversityBeijing, China.
Haijing
H
Zhang
Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal UniversityBeijing, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal UniversityBeijing, China; Institute of Chinese Materia Medica, China Academy of Chinese Medical SciencesBeijing, China.
Chunhui
C
Zhao
Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal UniversityBeijing, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal UniversityBeijing, China; Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Shandong Academy of ScienceJinan, China.
Cui
C
Lv
College of Resources Science Technology, Beijing Normal UniversityBeijing, China; Engineering Research Center of Sanqi Biotechnology and PharmaceuticalKunming, China.
Xiaoli
X
Liu
Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal UniversityBeijing, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal UniversityBeijing, China; College of Resources Science Technology, Beijing Normal UniversityBeijing, China.
Shijing
S
Du
Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal UniversityBeijing, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal UniversityBeijing, China; College of Resources Science Technology, Beijing Normal UniversityBeijing, China.
Zhi
Z
Li
Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal UniversityBeijing, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal UniversityBeijing, China; Institute of Chinese Materia Medica, China Academy of Chinese Medical SciencesBeijing, China; College of Resources Science Technology, Beijing Normal UniversityBeijing, China.
Yongyan
Y
Wang
Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal UniversityBeijing, China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal UniversityBeijing, China; College of Resources Science Technology, Beijing Normal UniversityBeijing, China; Engineering Research Center of Sanqi Biotechnology and PharmaceuticalKunming, China.
Wensheng
W
Zhang
amyloid β; axonal transport; geniposide; mitochondrial trafficking; spine morphology; synaptic loss