We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Cornel Iridoid Glycoside and Its Effective Component Regulate ATPase Vps4A/JNK to Alleviate Autophagy Deficit with Autophagosome Accumulation.
- Authors
Yang, Cui-Cui; Zheng, Ceng-Ceng; Luo, Yi; Guo, Kai-Wen; Gao, Dan; Zhang, Li; Li, Lin; Zhang, Lan
- Abstract
Improving autophagy-lysosome fusion has been considered a key method in the treatment of Alzheimer's disease (AD). Cornel iridoid glycoside (CIG) is extracted from Cornus officinalis and has been shown to promote the clearance of tau oligomers via the autophagy pathway. However, the mechanisms of CIG on autophagy deficits are not understood. Here, we found autophagy deficit and tau aggregation in the brains of P301S tau transgenic mice and MAPT cells edited using CRISPR-Cas9 technology. CIG decreased tau aggregation and alleviated autophagic markers involving the JNK/Beclin-1 signaling pathway which demonstrated CIG that might enhance lysosome formation by upregulating ATPase Vps4A expression. Knocking down VPS4A increased autophagosome accumulation and attenuated the effect of CIG on p62. In addition, CIG had no effect on tau oligomers but still inhibited the level of tau monomer in VPS4A knockout cells. The effective component (Sweroside, SWE) of CIG attenuated tau oligomers accumulation and increased Vps4A level but not CHMP2B. SWE could not change the level of tau oligomers in VPS4A knockout cells. In conclusion, CIG suppressed autophagosome accumulation by regulating the ATPase Vps4A/JNK. SWE is a core of active factors of CIG in Vps4A regulation. These findings suggest CIG may be a potential drug in AD treatment.
- Subjects
ALZHEIMER'S disease treatment; BIOLOGICAL models; BRAIN; NERVE tissue proteins; LYSOSOMES; AUTOPHAGY; HETEROCYCLIC compounds; ANIMAL experimentation; GLYCOSIDES; ADENOSINE triphosphatase; CELLULAR signal transduction; GENES; MICE
- Publication
American Journal of Chinese Medicine, 2022, Vol 50, Issue 6, p1599
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X22500677