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Compelling evidence from basic molecular biology has demonstrated the crucial role of microglia in the pathogenesis of Alzheimer's disease (AD). Microglia were believed to play a dual role in both promoting and inhibiting Alzheimer's disease progression. It is of great significance to regulate the function of microglia and make them develop in a favorable way. In the present study, we investigated the function of repressor element 1-silencing transcription factor (REST) in A β 1-42 -induced BV-2 cell dysfunction. We concluded that A β 1-42 could promote type I activation of BV-2 cells and induce cell proliferation, migration, and proinflammation cytokine TNF- α , IL-1 β , and IL-6 expression. Meanwhile, REST was upregulated, and nuclear translocalization took place due to A β 1-42 stimulation. When REST was knocked down by a specific short hairpin RNA (sh-RNA), BV-2 cell proliferation, migration, and proinflammation cytokine expression and secretion induced by A β 1-42 were increased, demonstrating that REST may act as a repressor of microglia-like BV-2 cell activation., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Tongya Yu et al.)