Cellular and Molecular Neurobiology最新文献

{"title":"Hypercholesterolemia Duration and Brain Area Determine Inflammatory Response Intensity and Apoptotic Mediator Activation in Apo E^-/-/LDLR^-/- Double-Knockout Mice.","authors":"Ewelina Czuba-Pakuła, Jolanta Ochocińska, Sebastian Głowiński, Alicja Braczko, Ryszard T Smoleński, Grażyna Lietzau, Przemysław Kowiański","doi":"10.1007/s10571-025-01562-0","DOIUrl":"10.1007/s10571-025-01562-0","url":null,"abstract":"<p><p>Hypercholesterolemia (Hch) is a risk factor for cerebrovascular and neurodegenerative diseases, manifesting with symptoms that vary depending on damage to specific brain regions. Hch triggers inflammatory responses and cell death. However, the progression of these processes in relation to the duration of Hch and the location of pathology in the central nervous system remains unclear. Therefore, we aimed to investigate (1) the impact of age and duration of Hch on neuroinflammatory responses and programmed cell death in the brain and (2) the intensity of these processes in various brain areas during Hch. In this study, we used 3-, 6-, and 12-month-old male Apo E^-/-/LDLR^-/- double-knockout mice and age-matched wild-type C57BL/6 mice (control group). Concentrations of cytokines IL-1β, IL-4, and IL-6, as well as apoptotic mediators AIF and Cas-3, were measured using enzyme-linked immunosorbent assay in the whole brain and separately in the prefrontal cortex (PFCx), hippocampus (HIP), and striatum (STR). The results showed that the Hch-induced release of cytokines IL-1β and IL-6, decreased expression of IL-4, and elevated level of apoptotic markers AIF and Cas-3 correlated with Hch duration. The inflammatory response and expression of apoptotic markers were more pronounced in the HIP and STR compared to the PFCx. Our results indicate a correlation between the neurodegenerative effects of Hch and its duration and highlight the varying susceptibility of different brain areas to Hch-induced damage.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"55"},"PeriodicalIF":3.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic Reticulum Stress Inhibition Promotes Mitophagy via Miro1 Reduction to Rescue Mitochondrial Dysfunction and Protect Dopamine Neurons in Parkinson's Disease.","authors":"Yuqi Wen, Zheng Han, Bao Wang, Chenxi Feng, Xvshen Ding, Yangni Li, Yan Lv, Xuelian Wang, Li Gao","doi":"10.1007/s10571-025-01575-9","DOIUrl":"10.1007/s10571-025-01575-9","url":null,"abstract":"<p><p>Both mitochondrial dysfunction and endoplasmic reticulum stress (ERS) have been implicated in the pathogenesis of Parkinson's disease (PD). However, the underlying regulatory mechanisms between ERS and mitochondrial dysfunction remain unclear. In the present study, we found that an in vitro model of Parkinson's disease (PD) induced by methyl-4-phenylpyridine (MPP⁺) showed increased intracellular peroxidation, leading to a significant increase in ERS. ER staining and immunofluorescence analysis of ERS-related proteins verified the presence of ERS, whereas transmission electron microscopy (TEM) showed complete depletion of ER. Notably, treatment with 4-phenylbutyric acid (4-PBA) to suppress ERS reduced apoptosis and concurrently reversed the ER micromorphology. Furthermore, 4-PBA alleviated mitochondrial dysfunction, as shown by increased mitochondrial membrane potential (MMP), upregulation of electron transport chain proteins, and restoration of mitochondrial integrity. Further studies revealed that the effect of 4-PBA could be attributed to the modulation of the mitochondrial Rho-GTPase 1 (Miro1)-mitophagy axis. In vivo experiments in Parkinson's disease models demonstrated that inhibiting ERS reduced dopaminergic neuron loss while improving cognitive and motor function. Collectively, these findings indicate that treatments targeting ERS may be potential candidates for treating PD.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"53"},"PeriodicalIF":3.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymer-Based Electrochemical Sensors for the Diagnosis of Neurodegenerative Diseases.","authors":"Qitong Zhang, Guangran Zhao, Shilin Wang, Yuxuan Song, Yuanzheng Sun","doi":"10.1007/s10571-025-01570-0","DOIUrl":"10.1007/s10571-025-01570-0","url":null,"abstract":"<p><p>Acute and chronic neurodegenerative diseases (NDs), including multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD), are characterized by neurodegeneration, which is the gradual malfunction and damage of neurons and axons in the central nervous system. Improved clinical diagnostic workups and the development and tracking of successful disease-modifying treatments are made possible by detecting appropriate neurodegenerative disease (ND) biomarkers. Important biomarkers, such as Tau proteins, amyloid-β, and α-synucleins, are essential for precise identification but are often evaluated using time-consuming, expensive, and traditional techniques like polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Due to its exceptional selectivity and sensitivity, electrochemical biosensing has become a popular, low-cost substitute for more conventional diagnostic methods. Nanoparticles in biosensors are particularly noteworthy because they improve electron transport and aid in immobilizing biorecognition components. Conducting polymers have shown great potential in the field of electrochemical sensing. Conducting polymers have shown great potential in electrochemical sensing. Additionally, research has shown that polypyrrole, polyaniline, poly(3,4-ethylenedioxythiophene), and poly(thiophene) are often regarded as among the best conducting polymers for fabricating electrochemical sensors. Moreover, a hydrogel biosensor allows for the detection of many parameters simultaneously with real-time monitoring, allowing for more accurate and timely tracking of multiple indicators of a patient. Hydrogel nano(bio)composite sensors that use electrochemical transduction methods to detect analytes are also available. Hydrogel-based polymer sensors for early-stage neurodegenerative diagnosis are examined in this review in a novel way. Afterward, we reviewed electrochemical sensors developed for detecting biomarkers related to diseases, including multiple sclerosis, Alzheimer's, Parkinson's, and Huntington's. There have also been developments devised to enhance efficacy of electrochemical diagnostic tools to address their limitations. In this respect, we have also reviewed many polymers used in electrochemical diagnosis of neurological disorders. Finally, we have also evaluated the limits and prospects of clinical trials involving these electrochemical means of diagnoses.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"52"},"PeriodicalIF":3.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening, Analysis, and Validation of Endoplasmic Reticulum Stress-Related DEGs in Epilepsy.","authors":"Sunyena Shi, Xu Feng, Zhan Cao, Lin Wang, Mingjian Sun, Ziyi Zhao, Wei Sun","doi":"10.1007/s10571-025-01567-9","DOIUrl":"10.1007/s10571-025-01567-9","url":null,"abstract":"<p><p>To investigate the relationship between Endoplasmic Reticulum Stress (ERS) and epilepsy, as well as their biological functions. We downloaded the GSE143272 dataset from the GEO database, identified differentially expressed genes (DEGs), and cross-analyzed them with ERS-related genes from GeneCards and the Molecular Signatures Database (MSigDB). Protein-protein interaction (PPI) networks were constructed, and Hub genes were screened. ROC curve analysis was conducted to assess the diagnostic utility of these genes, followed by qRT-PCR validation. This study identified a total of 83 ERS-related DEGs in epilepsy. PPI network analysis revealed eight feature genes: C-X-C motif chemokine ligand 8 (CXCL8), Toll-like receptor 4 (TLR4), Matrix metalloproteinase 9 (MMP9), Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), Prostaglandin-endoperoxide synthase 2 (PTGS2), Signal transducer and activator of transcription 1 (STAT1), B-cell lymphoma 2 (BCL2), and RELA proto-oncogene, NF-κB subunit (RELA). ROC curve analysis demonstrated that the combination of these eight feature genes exhibited the highest diagnostic potential. Among them, CXCL8 was the most valuable gene. qRT-PCR analysis showed that CXCL8 mRNA expression was significantly lower in the case group compared to the control group (P < 0.01). The results suggest that ERS is involved in physiological processes such as inflammation and neuronal apoptosis in epilepsy. This provides a bioinformatics evidence for exploring the biological functions and pathology of ERS in epilepsy, as well as serving as a reference for clinical diagnosis and potential therapeutic targets.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"51"},"PeriodicalIF":3.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herbal Interventions in Parkinson's Disease: A Systematic Review of Preclinical Studies.","authors":"Wanlin Zhao, Hailiang Cui, Jihong Liu, Hongyu Sun, Zijuan Zhang, Zhenqiang Zhang, Dongrui Ma","doi":"10.1007/s10571-025-01556-y","DOIUrl":"10.1007/s10571-025-01556-y","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra of the midbrain. With its incidence rising annually, the multi-mechanistic pathogenesis of PD presents new opportunities for the development of multi-target therapies. While previous studies have explored the therapeutic potential of natural products in PD, existing reviews often focus on single mechanisms or a limited number of compounds. While previous studies have explored the therapeutic potential of natural products in PD, existing reviews often focus on single mechanisms or a limited number of compounds. This article systematically evaluates preclinical studies published between 2018 and 2025, encompassing 32 bioactive components and 10 categories of traditional Chinese medicine (TCM) formulas. It highlights the therapeutic potential of TCM active ingredients for PD by examining key mechanisms, including oxidative stress, ferroptosis, neuroinflammation, gut microbiota imbalance, mitochondrial dysfunction, autophagy, and endoplasmic reticulum stress. By integrating these insights, this review provides an interdisciplinary perspective to guide the development of next-generation botanical drugs for PD.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"50"},"PeriodicalIF":3.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Role of Cuproptosis-Related Gene after Intracerebral Hemorrhage in Mice.","authors":"Xi Shen, Jiandong Zhu, Yuhang Gu, Jinxin Lu, Weiwei Zhai, Liang Sun, Jiang Wu, Zhengquan Yu","doi":"10.1007/s10571-025-01571-z","DOIUrl":"10.1007/s10571-025-01571-z","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a highly fatal form of stroke for which there are limited effective treatments. Cuproptosis, a newly discovered type of programmed cell death, has not yet been investigated in relation to ICH. Thus, the main goal of our study was to investigate the involvement of cuproptosis-related genes (CRGs) in predicting the early outcomes of ICH. We used datasets GSE228222 and GSE200575 from the Gene Expression Omnibus (GEO) database to identify and analyze differentially expressed genes (DEGs) between ICH samples and control samples from mice. From this analysis, seven cuproptosis-related DEGs (CuDEGs) were identified: pyruvate dehydrogenase E1 component subunit alpha (Pdha1), glutaminase (Gls), dihydrolipoamide dehydrogenase (Dld), pyruvate dehydrogenase E1 component subunit beta (Pdhb), dihydrolipoamide S-acetyltransferase (Dlat), metal regulatory transcription factor 1(Mtf1), and solute carrier family 31 member 1 (Slc31a1). Pathway enrichment analysis connected these genes to metabolic pathways, while immune cell infiltration analysis revealed increased macrophages and naive CD8 T cells alongside reduced NK resting cells and CD4 T cells in ICH samples. Verification through qRT-PCR and immunohistochemistry demonstrated a lower expression of CuDEGs in ICH samples. Of particular note, Gls, a gene significantly linked to both cuproptosis and immune regulation, exhibited reduced expression, possibly reflecting a protective response to limit glutamate production and mitigate neuronal damage. In summary, Gls emerges as a promising target for improving ICH outcomes by regulating cuproptosis and immune activity. This research provides novel insights into the molecular processes involved in ICH and suggests potential therapeutic approaches.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"48"},"PeriodicalIF":3.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethanol-Induced Depression: Exploring the Underlying Molecular Mechanisms.","authors":"Habibeh Mashayekhi-Sardoo, Fateme Razazpour, Zohreh Hakemi, Mahdiyeh Hedayati-Moghadam, Yousef Baghcheghi","doi":"10.1007/s10571-025-01569-7","DOIUrl":"10.1007/s10571-025-01569-7","url":null,"abstract":"<p><p>Ethanol consumption is widely recognized for its detrimental effects on mental health, particularly its association with depressive disorders. This narrative review aims to explore the intricate molecular mechanisms underlying ethanol-induced depression, synthesizing findings from preclinical and clinical studies. We begin by providing an overview of the relationship between chronic ethanol consumption and depression, highlighting compelling evidence from diverse populations. Subsequently, we delve into insights from animal models that elucidate the pathophysiological changes triggered by prolonged ethanol exposure. Key mechanisms identified include oxidative stress, which contributes to cellular damage; neuroinflammation, characterized by the activation of glial cells and altered cytokine profiles; and disruptions in neurotrophic factors that impair neuronal growth and survival. Furthermore, we discuss the induction of apoptosis in neural cells and the significant impact of ethanol on neurotransmitter receptor remodeling and regulation, leading to altered synaptic transmission. While substantial progress has been made in understanding these mechanisms, we also acknowledge the limitations of current research methodologies and call for further investigations to translate these findings into effective therapeutic strategies for individuals affected by ethanol-induced depression. This review ultimately underscores the need for a comprehensive understanding of the molecular underpinnings of ethanol's impact on mood disorders, paving the way for improved interventions and preventative measures.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"49"},"PeriodicalIF":3.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the Transforming Growth Factor β (TGF-β) on Brain Aneurysm Formation and Development: A Literature Review.","authors":"Kinga Sutkowska, Olga Martyna Koper-Lenkiewicz, Joanna Matowicka-Karna, Joanna Kamińska","doi":"10.1007/s10571-025-01572-y","DOIUrl":"10.1007/s10571-025-01572-y","url":null,"abstract":"<p><p>The mechanisms underlying the formation and rupture of intracranial aneurysms remain unclear. Rupture of the aneurysmal wall causes subarachnoid hemorrhage, with a mortality rate of 35-50%. Literature suggests that rupture is associated with the remodeling of the aneurysmal wall, including endothelial cell damage, smooth muscle cells (SMCs) proliferation, and inflammatory cell infiltration, particularly macrophages. Transforming growth factor β (TGF-β) is a multifunctional factor that plays a diverse role in cell growth and differentiation. It is crucial for strengthening vessel walls during angiogenesis and also regulates the proliferation of SMCs, indicating the potential involvement of TGF-β signaling in the pathogenesis and development of cerebral aneurysms. This review examines the complex role of TGF-β, its receptors, and signaling pathways in cerebral aneurysm formation and progression. Understanding the molecular mechanisms of TGF-β signaling in aneurysm development is vital for identifying potential therapeutic targets to prevent aneurysm rupture. Further research is necessary to fully elucidate the role of TGF-β in aneurysm pathophysiology, which could lead to the development of novel therapeutic strategies for aneurysm prevention and management, particularly in preventing subarachnoid hemorrhage.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"46"},"PeriodicalIF":3.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atorvastatin Protects Against the Macrophage/Microglia-Related Neuroinflammation via Inhibiting Lipocalin-2 in Mouse Experimental Intracerebral Hemorrhage Model.","authors":"Guangming Wang, Hongkang Hu, Junbin Liu, Xiaowei Fei, Yanan Dou, Li Wang, Lin Ying, Guohan Hu, Danfeng Zhang, Lei Jiang, Jialiang Wei","doi":"10.1007/s10571-025-01566-w","DOIUrl":"10.1007/s10571-025-01566-w","url":null,"abstract":"<p><p>There are few effective pharmacological interventions for intracerebral hemorrhage (ICH). Atorvastatin (Ato) has been shown to exert a substantial protective effect on ischemic stroke and is effective in alleviating neuroinflammation. Lipocalin-2 (LCN2), an important inflammation-regulating protein, has been demonstrated to play pivotal roles in post-ICH neuroinflammation. However, the exact role of Ato and whether LCN2 is involved after ICH remain largely unknown. In the current study, the BV2 (microglia) cell line, which was transfected with or without LCN2 for overexpression/interference, was co-cultured with primary cultured neurons and received blood infusion from C57BL/6 mice in vitro. For the in vivo study, atorvastatin was injected peritoneally into an ICH mouse model, and LCN2 specific knockout using the flox/cre system was performed in mice for mechanism study. Behavioral tests were conducted before ICH and on days 1, 3, and 7 post-ICH, and the brains and cultured cells were collected for protein, histological, and morphological studies. Our results showed that atorvastatin treatment alleviates neural damage and promotes neurological outcomes after ICH. Moreover, M1 activation and pro-inflammatory polarization are inhibited by atorvastatin. In both in vivo and in vitro models, the upregulation of LCN2 after ICH is substantially inhibited by atorvastatin. Studies on LCN2 transgenic mice and LCN2 overexpression/interference cells demonstrated that the suppression of macrophage/microglia (M/M) LCN2 participates in atorvastatin-mediated anti-neuroinflammation and neural protection effects. Therefore, our study suggests that atorvastatin treatment attenuates M/M-related neuroinflammation and protects neural recovery by down-regulating LCN2 after ICH. This study identified a potential novel therapeutic target for ICH treatment.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"47"},"PeriodicalIF":3.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Let-7 Family as a Mediator of Exercise on Alzheimer's Disease.","authors":"Shanbin Ke, Zhengqiong Liu, Yuwen Wan","doi":"10.1007/s10571-025-01559-9","DOIUrl":"10.1007/s10571-025-01559-9","url":null,"abstract":"<p><p>Memory loss, and behavioral impairments. Hallmark pathological features include amyloid-beta (Aβ) plaques, tau neurofibrillary tangles, chronic inflammation, and impaired neuronal signaling. Physical exercise is increasingly recognized as a non-pharmacological intervention to attenuate Alzheimer's disease (AD) risk and progression by enhancing neuroplasticity, improving mitochondrial function, and modulating immune responses. The let-7 family of microRNAs is critically involved in AD pathology. Elevated levels of let-7b and let-7e have been reported in the cerebrospinal fluid of AD patients, with let-7b levels correlating positively with total tau and phosphorylated tau concentrations. Overexpression of let-7a enhances Aβ-induced neurotoxicity, increases neuronal apoptosis by up to 45%, and alters autophagy-related signaling via the PI3K/Akt/mTOR pathway, as shown by 1.8-fold increases in LC3-II/I ratios and 2.2-fold upregulation of Beclin-1 expression. Exercise modulates let-7 expression in a tissue-specific and context-dependent manner. Aerobic training reduces skeletal muscle expression of let-7b-5p by 30-35%, while increasing its suppressor Lin28a by 40%, thereby improving mitochondrial respiration. Overall, modulation of let-7 by exercise influences neuronal survival, autophagy, and inflammation, offering a potential mechanism through which physical activity exerts neuroprotective effects in AD. Quantitative characterization of let-7 expression patterns may support its use as a diagnostic and therapeutic biomarker, though further research is needed to establish optimal modulation strategies.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"43"},"PeriodicalIF":3.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}