ACS Pharmacology and Translational Science最新文献

{"title":"Development of Delta Opioid Receptor Antagonists Which Prevent Alzheimer’s Disease-Like Pathology in the 5X-Familial Alzheimer’s Disease [5XFAD] Mouse Model","authors":"Parthasaradhireddy Tanguturi,&nbsp;Stefanie Mitchell,&nbsp;Omar Moukha-Chafiq,&nbsp;Sixue Zhang,&nbsp;John Tillotson,&nbsp;Subramaniam Ananthan,&nbsp;Corinne E. Augelli-Szafran and John M. Streicher*,&nbsp;","doi":"10.1021/acsptsci.5c00509","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00509","url":null,"abstract":"<p >Alzheimer’s Disease is a growing health concern, with no available disease-modifying treatments. A previous report suggested that a Delta Opioid Receptor (DOR) antagonist could prevent Alzheimer’s-like pathology; however, no DOR antagonists are clinically approved. We thus expanded on our previous structure–activity relationship work on morphinan scaffold DOR antagonists to generate and evaluate new DOR antagonist ligands. We identified a lead compound <b>12</b> (SRI-22136) with sub-nM DOR potency, high selectivity, and high inhibition of β-secretase activity. We further evaluated <b>12</b> in CD-1 mice, finding full antagonist efficacy at 1 mg/kg by the intraperitoneal route. We then tested the ability of <b>12</b> to prevent Alzheimer’s-like pathology in a 5XFAD transgenic mouse model, with daily treatment from 2 to 5 months of age. This treatment completely prevented Alzheimer’s-like pathology, including memory deficits, β-secretase activity, Aβ1–42 accumulation, and brain inflammatory markers. Together these results suggest <b>12</b> as a potential new lead compound to prevent Alzheimer’s Disease.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 9","pages":"3346–3370"},"PeriodicalIF":3.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Functional Dependence and Inhibition of the Bcl-2 Pro-Survival Proteins in a Wide Spectrum of Cancers toward Precision Medicine","authors":"Karson J. Kump,&nbsp;Ejaz Ahmad,&nbsp;Charles Foucar,&nbsp;Rita A. Avelar,&nbsp;Carlos Murga-Zamalloa,&nbsp;Matthew Lieberman,&nbsp;Malathi Kandarpa,&nbsp;Ahmed S. A. Mady,&nbsp;Analisa DiFeo,&nbsp;Lin Zhang,&nbsp;Sami Malek,&nbsp;Tycel Phillips,&nbsp;Ryan Wilcox,&nbsp;Dale Bixby,&nbsp;Moshe Talpaz and Zaneta Nikolovska-Coleska*,&nbsp;","doi":"10.1021/acsptsci.5c00088","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00088","url":null,"abstract":"<p >Introducing and integrating functional assays into clinical cancer care can further enhance the effectiveness of precision cancer medicine. Bcl-2 pro-survival proteins have emerged as promising targets across various cancers, with Venetoclax, a highly selective Bcl-2 inhibitor, being the first approved drug of this category. This study aims to explore BH3 profiling as a functional diagnostic to distinguish pro-survival dependence in a variety of human cancers to identify antiapoptotic Bcl-2 family protein dependencies and sensitivity to BH3 mimetics. The obtained results demonstrate that, in general, hematological cancer cell lines are sensitive to Bcl-2 or Mcl-1 inhibitors. Notably, certain lymphoma subtypes of B-cell and T-cell origin show preferential dependence on Bcl-2 and Mcl-1, respectively. These conclusions were supported and enhanced by follow-up studies of primary patient-derived samples. Immunohistochemistry of patient specimens supported the identified overexpression and functional involvement of Bfl-1 in T-cell lymphomas, highlighting a new potential precision therapy opportunity. Functional profiling of various solid tumor cell lines, including ovarian cancer PDX models, revealed that most solid tumors have a dependence on a combination of Bcl-2 family antiapoptotic proteins. Treatment with a combination of Bcl-xL and Mcl-1 inhibitors induced significant apoptosis in a majority of the tested solid tumor cell lines. The results of this study reveal a functional dependence on Bcl-2 antiapoptotic proteins in various cancers and offer more tailored strategies for utilizing BH3 mimetics in precision cancer therapy.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 9","pages":"2922–2935"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphoproteomic and Acetylomic Characterization of Colorectal Cancer Cells Treated with Kinase Inhibitors","authors":"Lei Zhao,&nbsp;Mingya Zhang,&nbsp;Jiafu Zhou,&nbsp;Xinglong Jia,&nbsp;Xiaotong Liang,&nbsp;Minjia Tan* and Jun-Yu Xu*,&nbsp;","doi":"10.1021/acsptsci.5c00398","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00398","url":null,"abstract":"<p >Kinase inhibitors have long been studied to be developed into therapeutic drugs or chemical probes, but their off-target effects in phosphoproteomics and acetylomics remain largely unexplored. Here, we provided a systematic molecular response to kinase inhibitors in the colorectal cancer cell line, including the proteomics, phosphoproteomics, and acetylomics. The results provided comprehensive kinase activity perturbations of each kinase inhibitor and presented unique pathway-level biological effects, mitochondrial functional perturbations, and kinase activity changes for inhibitors targeting the same pathway. Furthermore, we discovered the potential protein post-translational modification (PTM) crosstalk between lysine acetylation and protein phosphorylation. The study additionally proposed potential combination treatment strategies. In summary, this study presented in-depth and comprehensive analysis results of kinase inhibitor perturbations on the colorectal cancer cell line at proteomic, phosphoproteomic, and acetylomic landscapes.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 9","pages":"3269–3280"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Metabolism to Combat Neurodegeneration: Strategies for Reversing Age-Related Cognitive Decline","authors":"Smita Jain*,&nbsp;Reetuparna Acharya,&nbsp;Lavkush Verma and Aparna Chauhan,&nbsp;","doi":"10.1021/acsptsci.5c00077","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00077","url":null,"abstract":"<p >Age-related cognitive decline, a hallmark of neurodegenerative disorders such as Alzheimer’s disease, has been increasingly associated with metabolic dysregulation. Targeting metabolic pathways to enhance brain function and slow neurodegeneration presents a novel therapeutic approach. This review discusses key metabolic interventions that may reverse or delay cognitive decline. Mitochondrial dysfunction, oxidative stress, and impaired energy metabolism are central to neurodegenerative progression. Therapies aimed at boosting mitochondrial biogenesis, such as nicotinamide adenine dinucleotide (NAD⁺) precursors, adenosine monophosphate-activated protein kinase (AMPK) activators, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) modulators, have shown promise in improving neuronal energy balance and reducing oxidative damage. Metabolic interventions like caloric restriction, intermittent fasting, and ketogenic diets have demonstrated neuroprotective effects by enhancing insulin sensitivity, promoting autophagy, and shifting the brain’s energy reliance toward ketone bodies, which improves cognitive function. These strategies also mitigate neuroinflammation, a key driver of neuronal damage, by modulating immune responses and reducing the accumulation of toxic protein aggregates. Lipid metabolism also plays a crucial role in maintaining neuronal integrity. Enhancing lipid turnover, optimizing fatty acid profiles, and regulating cholesterol homeostasis may improve synaptic plasticity and reduce neuroinflammation, offering additional therapeutic avenues. By integrating current insights into metabolic regulation, this review underscores the potential of metabolic therapies to reverse or mitigate the cognitive decline associated with aging. Advancing our understanding of the intricate relationship between metabolism and neurodegeneration may pave the way for novel treatments targeting age-related cognitive impairment.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 9","pages":"2868–2886"},"PeriodicalIF":3.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid, Open-Source, and Automated Quantification of the Head Twitch Response in C57BL/6J Mice Using DeepLabCut and Simple Behavioral Analysis","authors":"Alexander D. Maitland,&nbsp;Nicholas R. Gonzalez,&nbsp;Donna Walther,&nbsp;Francisco Pereira,&nbsp;Michael H. Baumann and Grant C. Glatfelter*,&nbsp;","doi":"10.1021/acsptsci.5c00305","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00305","url":null,"abstract":"<p >Serotonergic psychedelics induce the head twitch response (HTR) in mice, an index of serotonin (5-HT) 2A receptor (5-HT_2A) agonism and a behavioral proxy for psychedelic effects in humans. Existing methods for detecting HTRs include time-consuming visual scoring, magnetometer-based approaches, and analysis of videos using semi-automated commercial software. Here, we present a new automated approach for quantifying HTRs from experimental videos using the open-source machine learning-based toolkits, DeepLabCut (DLC) and Simple Behavioral Analysis (SimBA). Pose estimation DLC models were trained to predict <i>X</i>,<i>Y</i> coordinates of 13 body parts of C57BL/6J mice using historical experimental videos of HTRs induced by various psychedelic drugs. Next, a nonoverlapping set of historical experimental videos was analyzed and used to train SimBA random forest behavioral classifiers to predict the presence of the HTR. The DLC + SimBA approach was then validated using a separate subset of visually scored videos. DLC + SimBA model performance was assessed at different video resolutions (50%, 25%, 12.5%) and frame rates (120, 60, 30 frames per second or fps). Our results indicate that HTRs can be quantified accurately at 50% resolution and 120 fps (precision = 95.45, recall = 95.56, <i>F</i>₁ = 95.51) or at lower frame rates and resolutions (i.e., 50% resolution and 60 fps). The best performing DLC + SimBA model combination was deployed to evaluate the effects of bufotenine, a tryptamine derivative with uncharacterized potency and efficacy in the modern HTR paradigm. Interestingly, bufotenine only induced elevated HTRs (ED₅₀ = 0.99 mg/kg, max counts = 24) when serotonin 1A receptors (5-HT_1A) were pharmacologically blocked and activity at other sites of action may also impact its pharmacological effects (e.g., serotonin transporter). HTR counts for a subset of 21 videos from bufotenine experiments were strongly correlated for DLC + SimBA vs visual scoring and semi-automated software detection methods (<i>r</i> = 0.98 and 0.99). Finally, the DLC + SimBA approach displayed high accuracy when compared to visual scoring of HTRs for three serotonergic psychedelic drugs with variable HTR frequencies (<i>r</i> = 0.99 vs mean visual scores from 3 blinded raters). In summary, the DLC + SimBA approach represents a modular, noninvasive, and open-source method of HTR detection from experimental videos with accuracy comparable to magnetometer-based approaches and greater speed than visual scoring.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 8","pages":"2694–2709"},"PeriodicalIF":3.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting α-Klotho Protein by Agmatine and Pioglitazone Is a New Avenue against Diabetic Nephropathy","authors":"Yasmena O. Azar*,&nbsp;Sherehan M. Ibrahim,&nbsp;Hala F. Zaki,&nbsp;Shimaa M. Elshazly and Ghada A. Badawi,&nbsp;","doi":"10.1021/acsptsci.5c00078","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00078","url":null,"abstract":"<p >Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM). Several mechanisms have been proposed for DN pathogenesis; however, it remains a progressive risk for DM patients. For the first time, the current study aimed to investigate the nephroprotective effects of agmatine and pioglitazone through modulating α-klotho, anti-ERS, anti-inflammatory, and antipyroptotic properties in ameliorating DN. A single intraperitoneal injection of streptozotocin (STZ) (52.5 mg/kg), preceded by nicotinamide (NA) (50 mg/kg, i.p.), induced DN. NA provided partial protection to insulin-secreting β-cells against the severe damage caused by STZ. Agmatine (100 mg/kg, i.p.) was injected daily for 6 weeks after modeling DN, either alone or in combination with pioglitazone (5 mg/kg, p.o.). DN rats showed a marked decrease in blood glucose (BG) levels, body weight, serum urea levels, serum creatinine (Cr) levels, and histopathological alterations, besides reducing renal α-klotho content associated with upregulating ATF4/IRE1α/NLRP3 renal content along with increasing HMGB1/NF-κB protein expression. On the contrary, agmatine and pioglitazone improved animals’ body weights, BG, serum urea, and Cr levels. Moreover, agmatine and pioglitazone inhibited renal NLRP3 content, reducing oxidative stress and inflammatory cascades. They also upregulated renoprotective α-klotho and decreased renal ATF4/IRE1α/TXNIP/NLRP3 content associated with a decrease in renal HMGB1/NF-κB protein expression. Briefly, besides its antidiabetic effect, agmatine, along with pioglitazone, shows promise as a treatment for DM and DN via mediating α-klotho/ERS/HMGB1/NF-κB/NLRP3 inflammasome signaling pathways.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 8","pages":"2493–2506"},"PeriodicalIF":3.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Development of Boron-Containing Small-Molecule Anticancer Agents","authors":"Yi-Miao Guo,&nbsp;Yue Cui,&nbsp;Le Yang* and Xue-Qiang Wang*,&nbsp;","doi":"10.1021/acsptsci.5c00238","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00238","url":null,"abstract":"<p >Small-molecule anticancer agents containing boron have attracted growing attention due to their unique chemical properties and promising anticancer activities. This review systematically summarizes recent advances in developing boron-based small-molecule agents, highlighting their molecular structures, mechanisms of action, and therapeutic applications. Specifically, it covers key categories such as boron neutron capture therapy (BNCT) agents, boron-based enzyme inhibitors, novel benzoxaborole derivatives, and boron-based reactive oxygen species (ROS)-targeting agents. The challenges associated with these boron-containing drugs, including limited tumor selectivity, suboptimal boron accumulation, and low bioavailability, are also highlighted. Additionally, it offers perspectives on future directions in the field, providing insights intended to guide ongoing research and development in boron-based anticancer therapies.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 8","pages":"2384–2400"},"PeriodicalIF":3.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Proteomics to Explore Biomarkers of Amyotrophic Lateral Sclerosis (ALS): Proof of Principle from Humanized SOD1 Mouse to Human ALS","authors":"Nitesh Sanghai*,&nbsp; and ,&nbsp;Geoffrey K. Tranmer,&nbsp;","doi":"10.1021/acsptsci.5c00403","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00403","url":null,"abstract":"<p >Amyotrophic lateral sclerosis (ALS) is a rare motor neurodegenerative disease affecting multiple cellular proteins during the progression of the disease. ALS was first discovered by Charcot in 1869, and since then, scientists have been unable to identify a singular cause of the disease. Further, there are no effective treatments available to cure ALS. The benchmark discovery of humanized preclinical SOD1 mouse models, which recapitulates the clinical and pathological phenotypes of human ALS, gives hope to medicinal chemists and neuroscientists around the globe that a suitable drug-like molecule can be discovered and translated into human beings as a means to slow down the progression of the disease. However, little success has been achieved until now in terms of finding an effective treatment for heterogenic and incurable ALS. One area marked for improvement is the use of semiquantitative, antibody-based targeted Western blotting (WB) experiments, which lack the power to analyze multiple cellular events within the entire dysregulated proteomic system. With the inconsistency of WB experiments, unexpected cellular pathways go undiscovered, and hence, loss of translation with no target engagement is seen from preclinical to human clinical ALS. Recent advancements in discovery-based quantitative proteomics have many advantages over WB. These innovative techniques could help solve the inherent problem in WB and their inability to discover multiple altered proteins with the added capability of longitudinal analysis in preclinical SOD1 models, further validating the findings in human ALS. Herein, we applied a holistic approach to summarize various reports on the use of proteomics in ALS from the published literature, and importantly, we found that using a discovery-based proteomics approach in SOD1 preclinical ALS models has revealed a more diverse and global picture of pathological proteins that affect multiple pathways during different stages of disease progression. Furthermore, we found that the proteomic profiling of the humanized SOD1 mouse model provided a proof of principle for translating the diverse pathological biomarker proteins identified in clinical human ALS cases. Moreover, we believe that advancements in the proteomics approach toward ALS biomarkers could bridge the gap between preclinical and clinical studies, enabling scientists worldwide to discover novel biomarkers and treatments that modify the progression of ALS.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 8","pages":"2415–2430"},"PeriodicalIF":3.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lacosamide Interaction with Expanded CGG Repeats RNA and Its Role in Modulating Poly-Glycine Protein-Mediated Toxicity in Fragile-X Tremor/Ataxia Syndrome","authors":"Krishna Singh,&nbsp;, ,&nbsp;Sakshi Shukla,&nbsp;, ,&nbsp;Aditi Pramod Kumari,&nbsp;, and ,&nbsp;Amit Kumar*,&nbsp;","doi":"10.1021/acsptsci.5c00198","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00198","url":null,"abstract":"<p >Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a severe neurodegenerative disorder triggered by expansions of CGG trinucleotide repeats in the <i>FMR1</i> gene. These extended trinucleotide RNA repeats [r(CGG)_exp] generate toxic homopolymeric poly-Glycine (polyG) proteins in neuronal cells through Repeat-Associated Non-AUG (RAN) translation and are also associated with RNA foci formation. This study examines the neuroprotective potential of Lacosamide, an antiepileptic drug, in targeting CGG repeat expansions associated with FXTAS. We employed a multidimensional approach, combining biophysical techniques, cellular assays, and a <i>Drosophila</i> model, to validate the selective interactions of Lacosamide with toxic CGG repeat RNA through a drug-repurposing strategy. Biophysical analyses, including Circular Dichroism (CD), Isothermal Titration Calorimetry (ITC), Electrophoretic Mobility Shift Assays (EMSA), and Nuclear Magnetic Resonance (NMR) spectroscopy, revealed Lacosamide’s binding affinity for GG mismatches within toxic CGG repeat RNA. Furthermore, Lacosamide treatment effectively mitigated polyG toxicity in FXTAS cellular and a <i>Drosophila</i> model of the disease. These affirmed the small molecule’s ability to reduce polyG aggregation-associated toxicity, thereby improving the diseased conditions. These findings suggest Lacosamide’s potential neuroprotective role in FXTAS, supporting further translational efforts for its clinical application to improve outcomes for patients affected by this debilitating disorder.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 10","pages":"3490–3508"},"PeriodicalIF":3.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pentacyclic Triterpenoid Maslinic Acid Promotes Hair Growth Comparable to Minoxidil: A New Insight on the Potential Involvement of Cilia Activity","authors":"Aprill Kee Oliva Mizushima,&nbsp;Meryem Bouhoute,&nbsp;Meriem Bejaoui,&nbsp;Farhana Ferdousi,&nbsp;Mitsutoshi Nakajima and Hiroko Isoda*,&nbsp;","doi":"10.1021/acsptsci.5c00189","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00189","url":null,"abstract":"<p >Maslinic acid is a pentacyclic triterpene component of olive extracts. In this study, we elucidated the effects of maslinic acid on hair growth and explored its underlying mechanisms. The topical application of maslinic acid stimulates hair growth in mice comparable to minoxidil, where an acceleration in anagen induction was observed. Moreover, treatment with maslinic acid led to increased protein levels of CTNNB1 and VEGF, and upregulated the mRNA expression of trichogenic genes, including <i>CTNNB1, ALPL,</i> and <i>FGF1</i>. Additionally, crucial pathways and biological processes involved in hair growth were activated such the Wnt, Notch, MAPK, and angiogenesis. Interestingly, <i>Iqcb1</i>, a ciliogenesis-promoting gene, was found to be upregulated by maslinic acid, leading us to explore the potential link between hair growth and cilia activity. Notably, inhibiting cilia activity resulted in the downregulation of <i>CTNNB1.</i> Altogether, our study suggests that maslinic acid stimulates hair growth through the Wnt/β-catenin pathway and introduces a possible mechanism involving ciliary gene activity.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 8","pages":"2586–2599"},"PeriodicalIF":3.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsptsci.5c00189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}