Vitamin K(2) protects against Aβ42-induced neurotoxicity by activating autophagy and improving mitochondrial function in Drosophila

OBJECTIVE: Alzheimer disease is characterized by progressive decline in cognitive function due to neurodegeneration induced by accumulation of Aβ and hyperphosphorylated tau protein. This study was conducted to explore the protective effect of vitamin K(2) against Aβ42-induced neurotoxicity. METHODS: Alzheimer disease transgenic Drosophila model used in this study was amyloid beta with the arctic mutation expressed in neurons. Alzheimer disease flies were treated with vitamin K(2) for 28 days after eclosion. Aβ42 level in brain was detected by ELISA. Autophagy-related genes and NDUFS3, the core subunit of mitochondrial complex I, were examined using real-Time PCR (RT-PCR) and western blot analysis. RESULTS: Vitamin K(2) improved climbing ability (P = 0.0105), prolonged lifespan (P < 0.0001) and decreased Aβ42 levels (P = 0.0267), upregulated the expression of LC3 and Beclin1(P = 0.0012 and P = 0.0175, respectively), increased the conversion of LC3I to LC3II (P = 0.0206) and decreased p62 level (P =0.0115) in Alzheimer disease flies. In addition, vitamin K(2) upregulated the expression of NDUFS3 (P = 0.001) and increased ATP production (P = 0.0033) in Alzheimer disease flies. CONCLUSION: It seems that vitamin K(2) protect against Aβ42-induced neurotoxicity by activation of autophagy and rescue mitochondrial dysfunction, which suggests that it may be a potential valuable therapeutic approach for Alzheimer disease.