Abstract: BACKGROUND: Neurodegenerative diseases are closely related to the imbalance of mitochondrial autophagy regulation. Previous studies by the research group have shown that lycium barbarum polysaccharide has neuroprotective effects, but whether it can improve the damage of SH-SY5Y cells induced by β-amyloid protein 1-42 by regulating mitochondrial autophagy is still unclear. 
OBJECTIVE: To explore the protective effect and mechanism of Lycium barbarum polysaccharide on SH-SY5Y cells induced by β-amyloid protein 1-42.  
METHODS: An Alzheimer's disease cell model was established by inducing SH-SY5Y cells with β-amyloid protein 1-42, and then intervening with Lycium barbarum polysaccharide. SH-SY5Y cells were divided into three groups: control group, β-amyloid protein 1-42 group (20 μmol/L β-amyloid protein 1-42 for 24 hours), and Lycium barbarum polysaccharide group (1 g/L Lycium barbarum polysaccharide was added 1 hour in advance to form a protective effect, and then 20 μmol/L β-amyloid protein 1-42 was added to intervene with Lycium barbarum polysaccharide for 24 hours). CCK8 assay was used to detect cell viability. Mitochondrial membrane potential was detected by JC-1. TUNEL staining was used to detect cell apoptosis. Immunofluorescence and western blot assay were used to detect the expression of synaptic, apoptosis, and mitophagy-related indicators.  
RESULTS AND CONCLUSION: (1) Compared with the control group, the cell viability of the β-amyloid protein 1-42 group decreased (P < 0.05); cell apoptosis rate increased (P < 0.05); mitochondrial membrane potential decreased (P < 0.05); the expressions of pro-apoptotic proteins Bax and Caspase3 increased (P < 0.05); the expression of anti-apoptotic protein Bcl-2 decreased (P < 0.05); the expression levels of synaptic-related proteins Syn and PSD-95 decreased (P < 0.05); the expression levels of mitochondrial autophagy-related proteins Pink1, LC3A/B, Parkin, and Beclin-1 decreased (P < 0.05); and the expression of P62 increased (P < 0.05). (2) Compared with the β-amyloid protein 1-42 group, the cell viability in the Lycium barbarum polysaccharide group was increased (P < 0.05); the apoptosis rate was decreased (P < 0.05); the mitochondrial membrane potential was increased (P < 0.05); the expression levels of Bax and Caspase3 were decreased (P < 0.05); the expression of Bcl-2 was increased (P < 0.05); the expressions of Syn and PSD-95 were increased (P < 0.05); the expression levels of Pink1, LC3A/B, Parkin, and Beclin-1 were increased (P < 0.05), and the expression of P62 was decreased (P < 0.05). These findings indicate that Lycium barbarum polysaccharide may inhibit β-amyloid protein 1-42-induced damage to SH-SY5Y cells by regulating mitophagy, reduce cell apoptosis, and increase neuronal synaptic plasticity. 

Key words: lycium barbarum polysaccharide, Alzheimer’s disease, SH-SY5Y cell, mitophagy, β-amyloid protein, apoptosis, engineered cells