PARP-1 is a multifunctional enzyme that regulates DNA repair, chromatin remodeling, inflammation and cell survival. Our previous study revealed that PARP-1 is required for maintaining normal level of neural stem cell proliferation. In the present study, we present evidence indicating that PARP-1 regulates neural stem cell proliferation by upregulating the expression of platelet-derived growth factor receptor alpha (PDGFR alpha). PARP-1 knockout neural stem cells exhibited striking downregulation of PDGFR alpha expression. We found that PARP-1 promotes the transcription of PDGFR alpha independently of its enzymatic activity. Overexpression of PDGFR alpha in the PARP-1 knockout neural stem cells reversed the proliferation defect of the knockout cells. Conversely, knockdown or blocking antibody of PDGFR alpha suppressed the proliferation of neural stem cells. In addition, blockade of PDGFR alpha increased cell death rate. Consistent with the downregulation of PDGFR alpha in the absence of PARP-1, PDGF-AA promoted proliferation of wild-type neural stem cells but not that of PARP-1 knockout cells. These results suggest that PARP-1 can control the neural stem cell proliferation by regulating the expression of PDGFR alpha. (C) 2020 Elsevier Inc. All rights reserved.