1.Inhibitory effect of curcumin on Aβ1-42-induced cell damage and mitochondrial pathway apoptosis
Shuyan LU ; Li YANG ; Xueling DAI ; Ping CHANG ; Zhaofeng JIANG ; Hanchang HUANG
Chinese Journal of Pharmacology and Toxicology 2017;31(2):138-144
OBJECTIVE To investigate the protective effect of curcumin on Aβ1-42 damaged cells. METHODS SH-SY5Y cells were cultured with Aβ1-4210μmol · L-1 in the absence or presence of curcumin 1, 5 or 10 μmol · L-1. Cell viability was assayed by MTT. Cell membrane damage was detected by the concentration of lactate dehydrogenase (LDH) in culture medium. Cell apoptosis was measured by flow cytometry with Annexin Ⅴ-FITC/PI staining. Mitochondrial membrane potential was characterized by fluorescence of JC-1 dye. Enzymatic activity of caspases-9 and-3 was measured by colorimetric assay. Protein expression of caspase-3 was detected by Western blotting. RESULTS Compared with vehicle control, the cell viability, concentration of LDH and both early and late apoptosis in Aβ1-4210 μmol · L-1 damaged group were decreased(P<0.01). However, the cell viability, release of LDH and both early and late apoptosis in curcumin group were promoted compared with that in Aβ1-4210μmol·L-1 damaged group. Curcumin inhibited Aβ1-42-induced depolarization of mitochondrial membrane potential(P<0.01), and attenuated Aβ1-42-induced activation of both caspases9 and caspases3 in a concentration-dependent manner, respectively(r=0.990, P<0.01; r=0.996, P<0.01). There were no significant differences in the above detected indexes between curcumin 10 μmol · L-1 group and vehicle control group. CONCLUSION Curcumin inhibits Aβ1-42-induced cell damage and apoptosis by promoting mitochondrial membrane potential and depressing the activation of caspases.
2. Research progress on the treatment of Alzheimer's disease based on the target of mammalian target of rapamycin
Zhun WANG ; Yuying SUN ; Hanchang HUANG ; Zhun WANG ; Yuying SUN ; Hanchang HUANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(12):1378-1390
Mammalian target of rapamycin (mTOR) regulates cell survival, proliferation, and metabolism. Alzheimer's disease (AD) is a common neurodegenerative disease with a complex pathogenesis and is closely related to aging. Studies have found that the pathological development of AD is often accompanied by changes in mTOR activity, but the role of mTOR in the pathogenesis of AD is not clear. In this paper, the complex of mTOR and its signaling pathways are first introduced, focusing on the effects of mTOR signaling pathways on synaptic plasticity and memory function, autophagy, βamyloid-β (Aβ), Tau protein and brain insulin resistance and other AD pathological features, secondly, the regulatory effects of mTOR signaling pathways in anti - aging and life prolongation are described, and finally the application of mTOR inhibitors in AD pathological research is introduced to provide new ideas for delaying and improving AD.