biostudies-literatureChen DNational Key R&D Program of China2804https://www.ebi.ac.uk/biostudies/studies/S-EPMC11943016biostudies-literatureUnknown26(6)In previous studies, we isolated a series of novel gentisides with nerve growth factor (NGF)-mimic activities from <i>Gentiana rigescens</i> Franch and conducted continuous structure-activity relationship (SAR) studies. Recently, a lead compound named TBG096 was discovered with significant NGF-mimic activity, low toxicity, and ability to pass through the blood-brain barrier (BBB). At the cell level, TBG096 exerts NGF-mimic activity by regulation of heat-shock cognate protein 70 (Hsc70) and downstream proteins. Subsequently, high-fat diet (HFD)-induced Alzheimer disease (AD) mouse models were used to evaluate the anti-AD efficacy of the compound. TBG096 significantly improved the memory dysfunction of AD mice at doses of 0.1, 5, and 20 mg/kg, respectively. In order to elucidate the mechanisInternational journal of molecular sciencesTBG096 Ameliorates Memory Deficiency in AD Mouse Model via Promoting Neurogenesis and Regulation of Hsc70/HK2/PKM2/LAMP2A Signaling Pathway.PMC119430162022YFE0104000Fasina OBQi JZeng JLin JManzoor MOhno HXiang LChen DfalseTBG096 Ameliorates Memory Deficiency in AD Mouse Model via Promoting Neurogenesis and Regulation of Hsc70/HK2/PKM2/LAMP2A Signaling Pathway.In previous studies, we isolated a series of novel gentisides with nerve growth factor (NGF)-mimic activities from <i>Gentiana rigescens</i> Franch and conducted continuous structure-activity relationship (SAR) studies. Recently, a lead compound named TBG096 was discovered with significant NGF-mimic activity, low toxicity, and ability to pass through the blood-brain barrier (BBB). At the cell level, TBG096 exerts NGF-mimic activity by regulation of heat-shock cognate protein 70 (Hsc70) and downstream proteins. Subsequently, high-fat diet (HFD)-induced Alzheimer disease (AD) mouse models were used to evaluate the anti-AD efficacy of the compound. TBG096 significantly improved the memory dysfunction of AD mice at doses of 0.1, 5, and 20 mg/kg, respectively. In order to elucidate the mechanis2025-01-01T00:00:00Z2025 Mar2025-07-02T03:04:46.55Z2025-07-02T03:04:46.55ZS-EPMC119430164014144510.3390/ijms26062804