Metabolic brain disease最新文献

{"title":"Unlocking the neuroprotective potential of peptide nucleic acids 5 (PNA5) in neurological diseases: molecular mechanisms to therapeutic approaches.","authors":"Pratyush Porel, Garry Hunjan, Navpreet Kaur, Vipul Sharma, Manpreet Kaur, Yukti Mittal, Ramandeep Kaur, Khadga Raj Aran","doi":"10.1007/s11011-025-01629-3","DOIUrl":"https://doi.org/10.1007/s11011-025-01629-3","url":null,"abstract":"<p><p>Peptide nucleic acids (PNAs) are synthetic nucleic acid analogues offering distinct structural and functional advantages over conventional RNA and DNA, positioning them as powerful molecules in molecular biology. Recently, PNAs have gained significant attention for their potential in the prevention and management of neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury (TBI), spinal cord injury (SCI), depression, and anxiety. PNA5, a specific PNA variant, is highly expressed in neocortical association regions, particularly in primates, and plays a critical role in high-level cognitive functions such as reasoning, decision-making, and problem-solving. It can form stable, sequence-specific hybridizations with nucleic acids, resist nuclease degradation, and efficiently cross cellular membranes, making them ideal candidates for targeting disease-related genes in the brain. PNA5 has shown neuroprotective properties by improving cognitive function, reducing neuroinflammation, and preserving the integrity of the blood-brain barrier (BBB). Additionally, it supports critical processes such as neural migration, axon guidance, and synaptogenesis, which are vital for maintaining proper brain function. This review explores the mechanisms by which PNAs, particularly PNA5, exert therapeutic effects in neurological disorders. It highlights their role in gene modulation, protein regulation, and potential strategies for enhancing PNA delivery to the central nervous system (CNS) and its related disorders.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"213"},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Acyl-CoA synthetase long-chain family member 4: a potential approach for the treatment of cerebral ischemia/reperfusion injury.","authors":"Nikita Patil, Lokesh Kumar Bhatt","doi":"10.1007/s11011-025-01638-2","DOIUrl":"https://doi.org/10.1007/s11011-025-01638-2","url":null,"abstract":"<p><p>Cerebral ischemia/reperfusion injury causes high rates of morbidity and death. Recent studies have shown that ferroptosis, a type of controlled cell death brought on by lipid peroxidation, worsens cerebral ischemia/reperfusion injury. Acyl-CoA synthetase long-chain family member 4 (ACSL4) has emerged as a crucial enzyme in lipid metabolism and ferroptosis in the context of ischemia/reperfusion injury, influencing neuronal cell death. Increased vulnerability to ferroptosis and worsening ischemia/reperfusion injury outcomes are linked to elevated ACSL4 levels. Comprehending the molecular processes underlying ACSL4-mediated ferroptosis may result in novel approaches to treating cerebral ischemia/reperfusion injury. The present review discusses ACSL4 as a potential target for treating cerebral ischemia/reperfusion injury, focusing on ACSL4-mediated ferroptosis and signal transduction.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"212"},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-134-5p/BDNF/TrkB/CREB signaling pathway involved in the depression-like behaviors in mice following exposure to benzo[a]pyrene.","authors":"Tingyi Zhao, Huan Li, Yunge Jia, Na Xia, Xin Li, Hongmei Zhang","doi":"10.1007/s11011-025-01637-3","DOIUrl":"https://doi.org/10.1007/s11011-025-01637-3","url":null,"abstract":"<p><p>Benzo[a]pyrene (B[a]P) is known to cause depression-like symptoms in mice, however, the mechanisms are still unclear. The present study aimed to establish a mouse model of depression-like behavior induced by B[a]P and to elucidate the possible underlying mechanisms. Forty robust male ICR mice were randomly categorized into 4 groups and received intraperitoneal injections (i.p.) of peanut oil or B[a]P at doses of 0.5, 2, or 10 mg/kg, 30 times over a period of 60 days. Behavioral assessments were conducted to evaluate depression-like symptoms, identify neuronal structural alterations and cellular apoptosis, and measure the protein levels of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphorylated TrkB (p-TrkB), cAMP-response element binding protein (CREB) and phosphorylated CREB (p-CREB) in the cerebral cortex. To further explore the regulatory role of miRNA, small RNA sequencing was performed in HT22 cells treated with B[a]P at concentrations of 0.2, 2, and 20 µM, which revealed the dysregulated miRNA expression profiles. The interaction between miR-134-5p and BDNF mRNA was examined, along with its inhibitory effects in both in vivo and in vitro contexts. Findings indicated that B[a]P exposure significantly induced depression-like behavior and neuronal damage in mice in a dose-dependent manner, in contrast to the controls, and was associated with a reduction in BDNF/TrkB/CREB signaling pathway proteins in the cerebral cortex. As compared to the respective controls, B[a]P exposure notably triggered an irregular miRNA expression profile (encompassing miR-10b-5p, miR-124-3p, miR-134-5p, and miR-155-5p) in both the cerebral cortex of mice and HT22 cells. Owing to its uniform alterations in expression profiles in vivo and in vitro, miR-134-5p was chosen as the target miRNA for follow-up mechanistic research employing a miR-134-5p inhibitor (at concentrations of 100 nM) in HT22 cells. Following a 48-hour in vitro treatment with B[a]P (20 µM), there was a notable reduction in proteins linked to the BDNF/TrkB/CREB signaling pathway, in contrast to DMSO controls. This decrease was markedly ameliorated in HT22 cells that had been transfected with the miR-134-5p inhibitor. The research uncovered the pivotal function of the BDNF/TrkB/CREB signaling pathway in B[a]P-induced depressive-like behavior in vivo, and showed a regulatory role of miR-134-5p in this pathway. These findings suggest a potential intervention target against the depression-like behaviors resulting from B[a]P exposure.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"210"},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective potential of carvacrol: restoration of oxidative balance and mitigation of brain injury markers in isoproterenol-induced rats.","authors":"Betül Bağcı, Şeyma Aydın, Elif Dalkılınç, Selim Çomaklı, Sefa Küçükler, Selçuk Özdemir","doi":"10.1007/s11011-025-01634-6","DOIUrl":"10.1007/s11011-025-01634-6","url":null,"abstract":"<p><p>This research investigated the protective properties of Carvacrol (CVC) against Isoproterenol (ISO)-induced oxidative stress, neuroinflammation, and mitochondrial dysfunction in rats. The findings showed that CVC treatment did not significantly modify baseline oxidative stress levels in healthy rats but successfully alleviated ISO-induced oxidative damage by augmenting antioxidant enzyme activity and diminishing lipid peroxidation, as demonstrated by a reduction in MDA levels. These findings indicate that CVC can reinstate antioxidant capability and reduce oxidative damage. Concerning neuroinflammation, ISO therapy markedly increased the expression of pro-inflammatory markers, including TNF-α, IL-1β, c-Fos, BDNF, Nfl, and GFP, signifying a robust inflammatory and damage response. The injection of CVC following ISO exposure markedly decreased the expression of these markers, suggesting that CVC may exert a neuroprotective effect by regulating the inflammatory response and mitigating neuronal and glial damage. CVC demonstrated a notable protective effect on mitochondrial integrity, evidenced by the decreased mRNA expression of mitochondrial damage markers, including NSE, s100B, CALP1, and CALM1 in the CVC-treated groups, showing that CVC mitigates mitochondrial dysfunction. The analysis revealed no significant alterations in the expression levels of Aβ40, pTau181, and tTau across all groups, indicating that these biomarkers were not substantially influenced by CVC treatment under the study's conditions. However, β-amyloid accumulation varied significantly between groups, highlighting the need for further research to explore CVC's potential implications in amyloid-related diseases. These findings endorse CVC's neuroprotective efficacy and therapeutic potential in neurological disorders associated with oxidative stress, inflammation, and mitochondrial impairment.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"211"},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of chitinase-3-like-1 protein in neurodegeneration.","authors":"Veerta Sharma, Thakur Gurjeet Singh","doi":"10.1007/s11011-025-01636-4","DOIUrl":"10.1007/s11011-025-01636-4","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDDs) are characterised by the progressive degeneration of neurons in the brain, resulting in impairments in memory, cognition, and motor abilities. Common pathological features include altered energy metabolism, neuroinflammation, death of neurons, aberrant protein aggregation, and synaptic dysfunction. Chitinase-3-like-1 (CHI3-L1) is an evolutionarily conserved protein involved in variety of biological processes such as neuroinflammation, tissue remodelling and angiogenesis. Elevated levels of CHI3-L1 have been detected in the cerebrospinal fluid and plasma of patients with NDDs, suggesting its involvement in disease progression. As a critical regulator of neuroinflammation, CHI3-L1 modulates the activity of astrocyte and microglia, causing the production of pro-inflammatory cytokines that worsens disease progression. In addition to its involvement in disease pathophysiology, it has emerged as a potential biomarker for the diagnosis and monitoring of neurological diseases. However, significant knowledge gaps persist regarding its molecular mechanisms, interactions with inflammatory mediators, and influence on blood-brain barrier integrity. Therefore, this review highlights the emerging role of CHI3-L1 in neurodegeneration and describes future research approaches targeted at unlocking its therapeutic potential in treating NDDs.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"209"},"PeriodicalIF":3.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhoifolin as a potential anxiolytic drug for the effects of nicotine withdrawal: beneficial effects on behavior, neuroinflammation, and oxidative stress.","authors":"Alaa M Hammad, Suhair Sunoqrot, Thanaa Al-Zuhd, Mohammed Waleed, Ali I M Ibrahim, F Scott Hall, Alaa R Al-Tamimi, Eveen Al-Shalabi","doi":"10.1007/s11011-025-01627-5","DOIUrl":"https://doi.org/10.1007/s11011-025-01627-5","url":null,"abstract":"<p><p>Cigarette smoke exposure induces oxidative stress and neuroinflammation, contributing to nicotine dependence and withdrawal-related anxiety. Rhoifolin (ROF), a naturally occurring flavonoid glycoside, possesses notable oxidative stress and inflammation reducing properties. This study investigated the potential ameliorative effects of ROF against cigarette smoke-induced neuroinflammation, oxidative damage, and withdrawal-induced anxiety-like behavior in rats. Rats were allocated into four treatment groups: a control group subjected only to ambient air; a nicotine (NIC) group exposed to cigarette smoke five days a week for seven weeks; a NIC/ROF group similarly exposed to smoke, but also treated with 20 mg/kg ROF daily for the last three weeks; and a ROF-only group treated with ROF while subjected to room air. Cigarette smoke exposure evoked anxiety during withdrawal periods, elevated levels of proinflammatory cytokines IL-1β and TNF-α, and a markedly reduced levels of key antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. ROF treatment significantly reversed these effects, reducing anxiety, lowering inflammatory markers, and restoring antioxidant enzyme activity to near-normal levels. Molecular modeling simulations showed a potential binding interaction for ROF at an allosteric pocket in each of the antioxidant enzyme structures, providing a potential mechanism by which ROF might act as an activator of these enzymes, thereby promoting antioxidant activity. Our findings suggest that ROF exhibits anxiolytic effects related to cigarette smoke exposure, likely mediated by its ameliorative role against inflammation and oxidative stress, supporting its potential role in improving behavioral outcomes of cigarette smoke withdrawal.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"208"},"PeriodicalIF":3.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypercholesterolemia, oxidative stress, and low-grade inflammation: a potentially dangerous scenario to blood-brain barrier.","authors":"Hémelin Resende Farias, Lílian Corrêa Costa-Beber, Fátima Theresinha Costa Rodrigues Guma, Jade de Oliveira","doi":"10.1007/s11011-025-01620-y","DOIUrl":"https://doi.org/10.1007/s11011-025-01620-y","url":null,"abstract":"<p><p>For more than a century, hypercholesterolemia has been linked to atherosclerotic cardiovascular disease. Notably, this metabolic condition has also been pointed out as a risk factor for neurodegenerative diseases, such as Alzheimer's disease (AD). Oxidative stress seems to be the connective factor between hypercholesterolemia and cardio and neurological disorders. By disturbing redox homeostasis, hypercholesterolemia impairs nitric oxide (NO) availability, an essential vasoprotective element, and jeopardizes endothelial function and selective permeability. The central nervous system (CNS) is partially protected from peripheral insults due to an arrangement between endothelial cells, astrocytes, microglia, and pericytes that form the blood-brain barrier (BBB). The endothelial dysfunction related to hypercholesterolemia increases the risk of developing cardiovascular diseases and also initiates BBB breakdown, which is a cause of brain damage characterized by neuroinflammation, oxidative stress, mitochondrial dysfunction, and, ultimately, neuronal and synaptic impairment. In this regard, we reviewed the mechanisms by which hypercholesterolemia-induced oxidative stress affects peripheral vessels, BBB, and leads to memory deficits. Finally, we suggest oxidative stress as the missing link between hypercholesterolemia and dementia.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"205"},"PeriodicalIF":3.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tong-Qiao-Huo-Xue Decoction mitigates post-stroke inflammatory response via suppression of the FIB-NLRP3 signaling pathway.","authors":"Ping Huang, Hao Sun, Yan Wang, Ning Wang","doi":"10.1007/s11011-025-01633-7","DOIUrl":"https://doi.org/10.1007/s11011-025-01633-7","url":null,"abstract":"<p><strong>Background: </strong> The post-stroke inflammatory response denotes the inflammatory damage inflicted upon brain tissue following stroke. Plasma fibrinogen (FIB) can permeate the compromised blood-brain barrier (BBB) after ischemic stroke, leading to the activation of the NLRP3 inflammasome. Tong-Qiao-Huo-Xue-Decoction (TQHXD), a traditional formula used to promote blood circulation and resolve blood stasis, has shown potential in this context. Nevertheless, the precise therapeutic mechanisms of TQHXD in mitigating cerebral ischemia-reperfusion injury remain to be fully elucidated. Objective. To examine the reparative effects and underlying mechanisms of TQHXD-CSF on inflammatory damage in BV-2 cells subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) injury. Methods. To establish an in vitro model of OGD/R injury and an inflammatory BV-2 cells model induced by FIB. The protective effects of TQHXD-CSF on OGD/R-injured cells were verified using CCK-8 and LDH assays. Immunofluorescence, SEM, Western blotting, and CHIP-PCR were employed to confirm that TQHXD reduces the inflammatory response by downregulating FIB levels. Pull-down and co-immunoprecipitation (CO-IP) assays were conducted to detect the interaction between FIB and NLRP3. Results. TQHXD-CSF can significantly inhibit the abnormal increase in LDH levels induced by OGD/R, enhance cell viability, and mitigate cell pyroptosis. Additionally, TQHXD-CSF reversed the marked upregulation of FIB, NLRP3, and GSDMD fluorescence intensity and protein expression caused by the FIB inflammation model, demonstrating an effect comparable to that of lumbrokinase, a fibrinolytic agent for FIB. Furthermore, it notably reduced the acetylation of H3 and H4 in the NLRP3 promoter. Importantly, the pull-down and CO-IP results indicated a robust binding affinity between FIB and NLRP3. Conclusion. TQHXD-CSF can inhibit inflammation by downregulating the FIB-NLRP3 pathway and exert a protective effect on BV-2 cells under OGD/R and FIB inflammatory injury.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"206"},"PeriodicalIF":3.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial activation as a hallmark of neuroinflammation in Alzheimer's disease.","authors":"Rasoul Ebrahimi, Shahrzad Shahrokhi Nejad, Mahdi Falah Tafti, Zahra Karimi, Seyyedeh Reyhaneh Sadr, Dana Ramadhan Hussein, Niki Talebian, Khadijeh Esmaeilpour","doi":"10.1007/s11011-025-01631-9","DOIUrl":"https://doi.org/10.1007/s11011-025-01631-9","url":null,"abstract":"<p><p>Microglial activation has emerged as a hallmark of neuroinflammation in Alzheimer's disease (AD). Central to this process is the formation and accumulation of amyloid beta (Aβ) peptide and neurofibrillary tangles, both of which contribute to synaptic dysfunction and neuronal cell death. Aβ oligomers trigger microglial activation, leading to the release of pro-inflammatory cytokines, which further exacerbates neuroinflammation and neuronal damage. Importantly, the presence of activated microglia surrounding amyloid plaques is correlated with heightened production of cytokines such as interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α), creating a vicious cycle of inflammation. While microglia play a protective role by clearing Aβ plaques during the early stages of AD, their chronic activation can lead to detrimental outcomes, including enhanced tau pathology and neuronal apoptosis. Recent studies have highlighted the dualistic nature of microglial activation, showcasing both inflammatory (M1) and anti-inflammatory (M2) phenotypes that fluctuate based on the surrounding microenvironment. Disruption in microglial function and regulation can lead to neurovascular dysfunction, further contributing to the cognitive decline seen in AD. Moreover, emerging biomarkers and imaging techniques are unveiling the complexity of microglial responses in AD, providing avenues for targeted therapeutics aimed at modulating these cells. Understanding the intricate interplay between microglia, Aβ, and tau pathology is vital for developing potential interventions to mitigate neuroinflammation and its impact on cognitive decline in AD. This review synthesizes current findings regarding microglial activation and its implications for AD pathogenesis, offering insights into future therapeutic strategies.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"207"},"PeriodicalIF":3.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salvianolic acid B ameliorates Aβ42 toxicity in Aβ42-expressing Drosophila model: behavioral and transcriptomic profiling.","authors":"Florence Hui Ping Tan, Ghows Azzam, Nazalan Najimudin, Shaharum Shamsuddin, Azalina Zainuddin, Mohd Shareduwan Mohd Kasihmuddin","doi":"10.1007/s11011-025-01625-7","DOIUrl":"https://doi.org/10.1007/s11011-025-01625-7","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is one of the most common neurodegenerative diseases worldwide. It is characterized by the accumulation of amyloid-beta (Aβ) plaques in which Aβ42 is the most toxic and aggressive species. This work investigates the possibility of salvianolic acid B (SalB), a natural compound with established neuroprotective activity, to counteract the Aβ42-induced toxicity in a Drosophila melanogaster model of AD. SalB's effect was assessed in the Aβ42-expressing Drosophila model by measuring three major AD-related behavioural symptoms: eye morphology (cytotoxicity), lifespan, and locomotor activity. The eye assay, longevity, and locomotion assays were employed, followed by RNA sequencing (RNA-seq) to identify molecular alterations following SalB treatment. Aβ42 expression in the Aβ42-expressing Drosophila model resulted in deformed eye morphology, reduced lifespan, and motor impairment. Treatment with SalB restored part of eye morphology, extended lifespan, and improved locomotion. RNA-seq revealed differential gene expression in oxidative phosphorylation, glutathione metabolism, and detoxification processes, suggesting the involvement of antioxidant defence in SalB-mediated neuroprotection. These findings indicate that SalB could be therapeutic for AD and other neurodegenerative disorders, possibly through the modulation of oxidative stress against Aβ42 toxicity. Further research is warranted to address its mechanisms and other uses in neurodegenerative therapy.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"204"},"PeriodicalIF":3.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}