Acta Pharmaceutica Sinica. B最新文献

{"title":"Fibroblast activation protein targeting radiopharmaceuticals: From drug design to clinical translation","authors":"Yuxuan Wu ,&nbsp;Xingkai Wang ,&nbsp;Xiaona Sun ,&nbsp;Xin Gao ,&nbsp;Siqi Zhang ,&nbsp;Jieting Shen ,&nbsp;Hao Tian ,&nbsp;Xueyao Chen ,&nbsp;Hongyi Huang ,&nbsp;Shuo Jiang ,&nbsp;Boyang Zhang ,&nbsp;Yingzi Zhang ,&nbsp;Minzi Lu ,&nbsp;Hailong Zhang ,&nbsp;Zhicheng Sun ,&nbsp;Ruping Liu ,&nbsp;Hong Zhang ,&nbsp;Ming-Rong Zhang ,&nbsp;Kuan Hu ,&nbsp;Rui Wang","doi":"10.1016/j.apsb.2025.07.009","DOIUrl":"10.1016/j.apsb.2025.07.009","url":null,"abstract":"<div><div>The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure–activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4511-4542"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis: A new target for anti-myocardial fibrosis","authors":"Xuewen Yang ,&nbsp;Yanwei Zhang ,&nbsp;Xiaoping Leng ,&nbsp;Yanying Wang ,&nbsp;Manyu Gong ,&nbsp;Dongping Liu ,&nbsp;Haodong Li ,&nbsp;Zhiyuan Du ,&nbsp;Zhuo Wang ,&nbsp;Lina Xuan ,&nbsp;Ting Zhang ,&nbsp;Han Sun ,&nbsp;Xiyang Zhang ,&nbsp;Jie Liu ,&nbsp;Tong Liu ,&nbsp;Tiantian Gong ,&nbsp;Zhengyang Li ,&nbsp;Shengqi Liang ,&nbsp;Lihua Sun ,&nbsp;Lei Jiao ,&nbsp;Ying Zhang","doi":"10.1016/j.apsb.2025.07.011","DOIUrl":"10.1016/j.apsb.2025.07.011","url":null,"abstract":"<div><div>Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4789-4806"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence that metformin promotes fibrosis resolution via activating alveolar epithelial stem cells and FGFR2b signaling","authors":"Yuqing Lv ,&nbsp;Yanxia Zhang ,&nbsp;Xueli Guo ,&nbsp;Baiqi He ,&nbsp;Haibo Xu ,&nbsp;Ming Xu ,&nbsp;Lihui Zou ,&nbsp;Handeng Lyu ,&nbsp;Jin Wu ,&nbsp;Pingping Zeng ,&nbsp;Saverio Bellusci ,&nbsp;Xuru Jin ,&nbsp;Chengshui Chen ,&nbsp;Young-Chang Cho ,&nbsp;Xiaokun Li ,&nbsp;Jin-San Zhang","doi":"10.1016/j.apsb.2025.07.023","DOIUrl":"10.1016/j.apsb.2025.07.023","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized <em>Sftpc</em> lineage-traced and <em>Fgfr2b</em> conditional knockout mice, along with BMP2/PPAR<em>γ</em> and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)—a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPAR<em>γ</em> inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, <em>Fgfr2b</em> deletion in <em>Sftpc</em> lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPAR<em>γ</em> pathways.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4711-4729"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deubiquitinase OTUD6A alleviates acetaminophen-induced liver injury by targeting EZH2 to reduce cell death in hepatocytes","authors":"Yanni Zhao ,&nbsp;Tianyang Jin ,&nbsp;Tingxin Xu ,&nbsp;Yi Fang ,&nbsp;Qingsong Zheng ,&nbsp;Wu Luo ,&nbsp;Weiwei Zhu ,&nbsp;Yue Chen ,&nbsp;Jiong Wang ,&nbsp;Yi Chen ,&nbsp;Wei Zuo ,&nbsp;Lijiang Huang ,&nbsp;Guang Liang ,&nbsp;Yi Wang","doi":"10.1016/j.apsb.2025.06.027","DOIUrl":"10.1016/j.apsb.2025.06.027","url":null,"abstract":"<div><div>Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4772-4788"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PARylated RACK1/HIF-1α axis: A novel mechanism in acute kidney injury and therapeutic promise","authors":"Jiafa Ren ,&nbsp;Steven D. Crowley","doi":"10.1016/j.apsb.2025.08.004","DOIUrl":"10.1016/j.apsb.2025.08.004","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4970-4971"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural vaccine adjuvants from traditional Chinese medicines: Mechanisms to applications","authors":"Xiaoyuan Fan ,&nbsp;Fengxiang Liu ,&nbsp;Fei Sun ,&nbsp;Yiyang Wang ,&nbsp;Wenwen Shen ,&nbsp;Shujun Wang ,&nbsp;Jin Sun ,&nbsp;Kaiyuan Wang","doi":"10.1016/j.apsb.2025.06.021","DOIUrl":"10.1016/j.apsb.2025.06.021","url":null,"abstract":"<div><div>With the rapid advancement of vaccines, the research and application of vaccine adjuvants have garnered significant attention. Despite the development of numerous vaccine adjuvants, their applications in human vaccines remain limited due to either insufficient efficacy or severe side effects. Consequently, there is growing interest in developing bioactive compounds derived from traditional Chinese medicines (TCMs) as vaccine adjuvants, owing to their natural biocompatibility, diversity, and safety. Here, we systematically review the current application status and potential value of TCM-based bioactive compounds in vaccine adjuvants. Firstly, we elaborate on the types and characteristics of active ingredients, such as polysaccharides, saponins, flavonoids, acids, and alkaloids. The mechanisms by which these compounds function as vaccine adjuvants are then discussed, including their roles in enhancing humoral immunity, cellular immunity, and relieving the immune suppression in the microenvironment. Additionally, we summarize the current strategies for structural modification and platform optimization to adapt to different application scenarios. Finally, we offer insights into the future development directions for these potential adjuvants, highlighting research priorities, technical approaches, and application prospects. In conclusion, natural vaccine adjuvants derived from TCMs present broad application prospects and hold promise for future vaccine development.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4644-4672"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARylation promotes acute kidney injury via RACK1 dimerization-mediated HIF-1α degradation","authors":"Xiangyu Li ,&nbsp;Xiaoyu Shen ,&nbsp;Xinfei Mao ,&nbsp;Yuqing Wang ,&nbsp;Yuhang Dong ,&nbsp;Shuai Sun ,&nbsp;Mengmeng Zhang ,&nbsp;Jie Wei ,&nbsp;Jianan Wang ,&nbsp;Chao Li ,&nbsp;Minglu Ji ,&nbsp;Xiaowei Hu ,&nbsp;Xinyu Chen ,&nbsp;Juan Jin ,&nbsp;Jiagen Wen ,&nbsp;Yujie Liu ,&nbsp;Mingfei Wu ,&nbsp;Jutao Yu ,&nbsp;Xiaoming Meng","doi":"10.1016/j.apsb.2025.07.019","DOIUrl":"10.1016/j.apsb.2025.07.019","url":null,"abstract":"<div><div>Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1<em>α</em> (HIF-1<em>α</em>) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), <strong>A19</strong>, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1<em>α</em> axis could be a promising therapeutic target for AKI treatment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4673-4691"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of powerful multifaceted antioxidant for combating oxidative stress associated with neurodegenerative disorders","authors":"Juhee khan ,&nbsp;Prabir kumar Gharai ,&nbsp;Shubham Garg ,&nbsp;Sanju Gupta ,&nbsp;Mohammad Umar Arshi ,&nbsp;Rathnam Mallesh ,&nbsp;Surajit Ghosh","doi":"10.1016/j.apsb.2025.04.024","DOIUrl":"10.1016/j.apsb.2025.04.024","url":null,"abstract":"<div><div>Amidst the tangled web of neurons, antioxidants stand as silent sentinels, shielding the delicate threads from the raging storm of oxidative stress in the realm of neurological affliction. Herein, we showcased an innovative design strategy to develop a novel powerful antioxidant small molecule (AOX), designed with the synergistic integration of EGCG (epigallocatechin gallate), gallic acid, and coupled with the metal-chelating capabilities of 8-hydroxy quinoline functional moieties that exhibit multifunctional activity in combating oxidative stress <em>via</em> activating the anti-oxidative, anti-apoptotic and anti-inflammatory activity, showcasing the potential for a transformative impact in neuroprotection from oxidative insults. Our work addresses oxidative stress in neuronal systems by providing a thorough examination of oxidative stress caused by hydrogen peroxide in PC12 cell line-derived neurons by shedding light on the antioxidative mechanisms orchestrated by our novel small molecule. Particularly our designed molecule (AOX) provides neuroprotection by mitigating mitochondrial impairment and activating the Nrf2/ARE (nuclear factor erythroid 2-related factor 2/antioxidant response element) pathway and it also demonstrates remarkable resilience against neuroinflammation, as evidenced by minimal alterations in neuroinflammatory markers such as GFAP, IBA1, and S100<em>β</em> in a transient bilateral common carotid artery occlusion (tBCCAO) ischemic stroke model.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4844-4871"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author correction to “Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways” [Acta Pharm Sin B 15 (2025) 2024–2038]","authors":"Meiyu Shang ,&nbsp;Jingwen Ning ,&nbsp;Caixia Zang ,&nbsp;Jingwei Ma ,&nbsp;Yang Yang ,&nbsp;Zhirong Wan ,&nbsp;Jing Zhao ,&nbsp;Yueqi Jiang ,&nbsp;Qiuzhu Chen ,&nbsp;Yirong Dong ,&nbsp;Jinrong Wang ,&nbsp;Fangfang Li ,&nbsp;Xiuqi Bao ,&nbsp;Dan Zhang","doi":"10.1016/j.apsb.2025.06.017","DOIUrl":"10.1016/j.apsb.2025.06.017","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Page 4972"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytic dopamine D1 receptor modulates glutamatergic transmission and synaptic plasticity in the prefrontal cortex through d-serine","authors":"Yanan Yin ,&nbsp;Jian Hu ,&nbsp;Haipeng Wu ,&nbsp;Xinyu Yang ,&nbsp;Jingwen Qi ,&nbsp;Lang Huang ,&nbsp;Zhengyi Luo ,&nbsp;Shiyang Jin ,&nbsp;Nengyuan Hu ,&nbsp;Zhoucai Luo ,&nbsp;Tong Luo ,&nbsp;Hao Chen ,&nbsp;Xiaowen Li ,&nbsp;Chunhua Yuan ,&nbsp;Shuji Li ,&nbsp;Jianming Yang ,&nbsp;Yihua Chen ,&nbsp;Tianming Gao","doi":"10.1016/j.apsb.2025.07.034","DOIUrl":"10.1016/j.apsb.2025.07.034","url":null,"abstract":"<div><div>The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the <em>Drd1</em> in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas <em>Drd1</em> deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of <span>d</span>-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of <span>d</span>-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through <span>d</span>-serine, and may shed light on the treatment of mental disorders.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4692-4710"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}