biostudies-literatureHu YScience and Technology Support Program of Jiangsu ProvinceKey Laboratory in Science and Technology Development Project of SuzhouNational Natural Science Foundation of ChinaSuzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases, the Interdisciplinary Basic Frontier Innovation Program of Suzhou Medical College of Soochow UniversityMOE Key Laboratory of Geriatric Diseases and Immunology140https://www.ebi.ac.uk/biostudies/studies/S-EPMC11977062biostudies-literatureUnknown82(1)Parkinson's disease (PD) is a common neurodegenerative movement disorder characterized by dopaminergic neuron loss in the substantia nigra pars compacta and striatal dopamine depletion. The NUS1 gene, which encodes the neurite outgrowth inhibitor B receptor (NgBR), has been recently identified as a novel risk gene for PD. However, its roles and mechanism in neurodegeneration are still unclear. Here, we demonstrate that NgBR deficiency triggers neuronal damage through a novel KAT7/RFX1/FGF1 axis. RNA sequencing and experimental verification revealed that NgBR depletion downregulates expression and secretion of fibroblast growth factor 1 (FGF1), which led to inactivation of the PI3K/AKT signaling pathway. Mechanistically, NgBR deletion suppresses lysine acetyltransferase 7 (KAT7) expression,Cellular and molecular life sciences : CMLSLoss of NgBR causes neuronal damage through decreasing KAT7-mediated RFX1 acetylation and FGF1 expression.PMC11977062YXY2303023CXZX202231JYN202401SZ20240013227103932170987, 32471047Ren HHu YLiu LGuo JHong YCao YYang PMa YTang BWang GfalseLoss of NgBR causes neuronal damage through decreasing KAT7-mediated RFX1 acetylation and FGF1 expression.Parkinson's disease (PD) is a common neurodegenerative movement disorder characterized by dopaminergic neuron loss in the substantia nigra pars compacta and striatal dopamine depletion. The NUS1 gene, which encodes the neurite outgrowth inhibitor B receptor (NgBR), has been recently identified as a novel risk gene for PD. However, its roles and mechanism in neurodegeneration are still unclear. Here, we demonstrate that NgBR deficiency triggers neuronal damage through a novel KAT7/RFX1/FGF1 axis. RNA sequencing and experimental verification revealed that NgBR depletion downregulates expression and secretion of fibroblast growth factor 1 (FGF1), which led to inactivation of the PI3K/AKT signaling pathway. Mechanistically, NgBR deletion suppresses lysine acetyltransferase 7 (KAT7) expression,2025-01-01T00:00:00Z2025 Apr2025-07-05T03:04:51.259Z2025-07-05T03:04:51.259ZS-EPMC119770624019283610.1007/s00018-025-05660-6