Molecular Neurobiology最新文献_第4页

Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative Diseases and Targeted Therapy. 小胶质细胞中的葡萄糖代谢重编程：对神经退行性疾病和靶向治疗的影响。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-07-01 Epub Date: 2025-02-22 DOI: 10.1007/s12035-025-04775-y

Mengqi Fang, Yuan Zhou, Keren He, Yangyuxiao Lu, Fangfang Tao, Hong Huang

{"title":"Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative Diseases and Targeted Therapy.","authors":"Mengqi Fang, Yuan Zhou, Keren He, Yangyuxiao Lu, Fangfang Tao, Hong Huang","doi":"10.1007/s12035-025-04775-y","DOIUrl":"10.1007/s12035-025-04775-y","url":null,"abstract":"As intrinsic immune cells in the central nervous system, microglia play a crucial role in maintaining brain homeostasis. Microglia can transition from homeostasis to various responsive states in reaction to different external stimuli, undergoing corresponding alterations in glucose metabolism. In neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), microglial glucose metabolic reprogramming is widespread. This reprogramming leads to changes in microglial function, exacerbating neuroinflammation and the accumulation of pathological products, thereby driving the progression of neurodegeneration. This review summarizes the specific alterations in glucose metabolism within microglia in AD, PD, ALS, and MS, as well as the corresponding treatments aimed at reprogramming glucose metabolism. Compounds that inhibit key glycolytic enzymes like hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2), or activate regulators of energy metabolism such as AMP-activated protein kinase (AMPK), have shown significant potential in the treatment of various neurodegenerative diseases. However, current research faces numerous challenges, including side effects and blood-brain barrier (BBB) penetration of compounds. Screening relevant drugs from natural products, especially flavonoids, is a reliable approach. On the one hand, longtime herbal medical practices provide a certain degree of assurance regarding clinical safety, and their chemical properties contribute to effective BBB permeability. On the other hand, the concurrent anti-tumor and anti-neuroinflammatory activities of flavonoids suggest that regulation of glucose metabolism reprogramming might be a potential common mechanism of action. Notably, considering the dynamic nature of microglial metabolism, there is an urgent need to develop technologies for real-time monitoring of glucose metabolism processes, which would significantly advance research in this field.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8204-8221"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular Stem Cell Therapy for Treating Traumatic Brain Injury: Strategies for Enhancement of Therapeutic Efficacy. 细胞干细胞治疗创伤性脑损伤：提高治疗效果的策略。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-07-01 Epub Date: 2025-02-25 DOI: 10.1007/s12035-025-04778-9

Ali Q Khazaal, Haneen M Ismaeel, Pike See Cheah, Norshariza Nordin

{"title":"Cellular Stem Cell Therapy for Treating Traumatic Brain Injury: Strategies for Enhancement of Therapeutic Efficacy.","authors":"Ali Q Khazaal, Haneen M Ismaeel, Pike See Cheah, Norshariza Nordin","doi":"10.1007/s12035-025-04778-9","DOIUrl":"10.1007/s12035-025-04778-9","url":null,"abstract":"Traumatic brain injury (TBI) influences a considerable population globally. TBI notably impacts both fatalities and disabilities worldwide. The mortality related to TBI is a significant concern in public health, affecting persons across various age groups and demographic profiles. More research and preventative interventions are required to alleviate TBIs' effects and optimize patient outcomes. Stem cell (SC) treatment exhibits promise as a viable strategy for addressing TBI due to its capacity to possibly restore or regenerate the compromised cells within the central nervous system. Additionally, it can influence the inflammatory response and increase neurogenesis and neuroplasticity. Increasing evidence has shown that SC transplantation has the potential to enhance functional recovery and decrease the extent of lesions in animal models of TBI. Nevertheless, several hurdles and ambiguities persist in determining the most effective source, dosage, administration method, timing, and mechanism of action for SC treatment for TBI. Further investigation is required to prove the safety and effectiveness of SC treatment for TBI in human subjects. This review brings insight into the strategies for utilizing SCs as cellular therapy for TBI, mainly based on preclinical investigations and TBI-induced animal models. In addition, this study also addresses many elements related to cell transfusion in the context of TBI, including considerations of cell amount, method, and timing. Integrating biomaterials and genetically altering SCs as potential strategies to enhance therapeutic efficacy are also presented. We also describe the potential of SCs in treating TBI and evaluate the effectiveness of cellular therapy and its corresponding outcomes.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8359-8380"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thoracic Spinal Cord Contusion Impacts on Lumbar Enlargement: Molecular Insights. 胸段脊髓挫伤对腰椎增大的影响：分子观察。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-07-01 Epub Date: 2025-02-27 DOI: 10.1007/s12035-025-04794-9

Ilyas Kabdesh, Olga Tutova, Elvira Akhmetzyanova, Anna Timofeeva, Aizilya Bilalova, Yana Mukhamedshina, Yuri Chelyshev

{"title":"Thoracic Spinal Cord Contusion Impacts on Lumbar Enlargement: Molecular Insights.","authors":"Ilyas Kabdesh, Olga Tutova, Elvira Akhmetzyanova, Anna Timofeeva, Aizilya Bilalova, Yana Mukhamedshina, Yuri Chelyshev","doi":"10.1007/s12035-025-04794-9","DOIUrl":"10.1007/s12035-025-04794-9","url":null,"abstract":"Spinal cord injury (SCI) is characterized by macrostructural pathological changes in areas significantly distant from the primary injury site. The causes and mechanisms underlying these distant changes are still being explored. Identifying the causes and mechanisms of these changes in the lumbar spinal cord is particularly important for restoring motor function, especially in cases of injury to the proximal thoracic or cervical regions. This is because the lumbar region contains neural networks that play a crucial role in comprehensive locomotor outcomes. In our study, we investigated the changes in the rat lumbar spinal cord following a thoracic contusion injury. We observed an increased expression of osteopontin (OPN) in large neurons and a higher number of interneurons co-expressing parvalbumin and OPN within lamina IX of the ventral horns (VH) in the gray matter of the lumbar spinal cord post-injury. Additionally, here we noted an increased co-localization of the glial fibirillary acidic protein and S100A10 protein, a specific marker of reactive A2 astrocytes. Our findings also include changes in the expression and content of glypicans in the gray matter, a significant rise in neurotoxic M1 microglia/macrophages, alterations in the cytokine profile, and a decreased expression of the extracellular matrix molecules tenascin R and aggrecan. This research highlights the complex pathological processes occurring far from the site of SCI and attempts to provide insights into the mechanisms involving the entire spinal cord in the response to such an injury.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8551-8567"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Empagliflozin Inhibits Neuronal Ferroptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation by Activating the Nrf2/HO-1 Pathway. 恩格列净通过激活Nrf2/HO-1通路抑制氧-葡萄糖剥夺/再氧化诱导的神经元铁凋亡。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-07-01 Epub Date: 2025-03-05 DOI: 10.1007/s12035-025-04800-0

Jialiang Ma, Hongxia Wang, Juan Jia, Ting Tao, Lingzhi Shan, Shougang Sun, Manxia Wang

{"title":"Empagliflozin Inhibits Neuronal Ferroptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation by Activating the Nrf2/HO-1 Pathway.","authors":"Jialiang Ma, Hongxia Wang, Juan Jia, Ting Tao, Lingzhi Shan, Shougang Sun, Manxia Wang","doi":"10.1007/s12035-025-04800-0","DOIUrl":"10.1007/s12035-025-04800-0","url":null,"abstract":"The impact of empagliflozin on OGD/R-induced ferroptosis in neurons is still unclear. This study aims to explore whether ferroptosis is associated with OGD/R-induced neuronal injury and the effect of empagliflozin on the ferroptosis effect of OGD/R-treated neurons. Western blotting, immunofluorescence, and RT-qPCR were used to detect the protein and mRNA levels of GPX4, Nrf2, and HO-1. ELISA, flow cytometry, and confocal microscopy were applied to analyze oxidative stress. Transmission electron microscopy and CCK-8 were used to determine the degree of ferroptosis in neurons. We observed a reduction in GPX4 levels and an increase in Nrf2 and HO-1 levels in OGD/R related neurons HT-22 cells. Notably, OGD/R elevates lipid peroxidation accumulation, ROS, Fe2+, and MDA levels while reducing GSH levels and decreasing mitochondrial membrane potential, leading to abnormal mitochondrial structure and eventual neuronal ferroptosis. Empagliflozin activates the Nrf2/HO-1 signaling pathway, enhances cellular antioxidant capacity, inhibits lipid peroxidation in OGD/R-treated neurons, and restores cellular iron homeostasis. In addition, empagliflozin can significantly reverse ferroptosis in OGD/R-treated neurons, and overexpression of Nrf2 combined with empagliflozin further inhibits ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be an essential cause of OGD/R-related neuron death. Empagliflozin exhibits a protective influence against OGD/R-induced ferroptosis by activating the Nrf2/HO-1 pathway.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8768-8781"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nuclear MicroRNA-124-3p Promotes Neurite Outgrowth After Spinal Cord Injury by Enhancing Cttn Transcription. 核MicroRNA-124-3p通过增强Cttn转录促进脊髓损伤后神经突生长。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-07-01 Epub Date: 2025-03-05 DOI: 10.1007/s12035-025-04813-9

Jin Yang, Junjie Dong, Haotian Li, Zhiqiang Gong, Bing Wang, Kaili Du, Chunqiang Zhang, Lingqiang Chen

{"title":"Nuclear MicroRNA-124-3p Promotes Neurite Outgrowth After Spinal Cord Injury by Enhancing Cttn Transcription.","authors":"Jin Yang, Junjie Dong, Haotian Li, Zhiqiang Gong, Bing Wang, Kaili Du, Chunqiang Zhang, Lingqiang Chen","doi":"10.1007/s12035-025-04813-9","DOIUrl":"10.1007/s12035-025-04813-9","url":null,"abstract":"The outgrowth of motor neurons needs to be enhanced for the efficient recovery of sensory and movement abilities after nerve injury. The microRNA miR-124-3p can repair spinal cord injury (SCI) and promote neurite outgrowth. In this study, we aimed to investigate the effect of miR-124-3p on neurite outgrowth and the mechanism underlying its effect on SCI. Rats with SCI were intrathecally injected with agomiR-124 (miR-124-3p agomiR) for 14 days. The agomiR-124 improved locomotor functions were observed with open-field scoring systems. The levels of miR-124-3p and Cortactin across three weeks, and neuronal biomarkers NF200, Tuj1, Map2 and NeuN post 6 weeks were reduced in rats with SCI, which were reverted with agomiR-124 treatment. The wound scratch assay showed that agomiR-124 enhanced outgrowth of neurites in PC12 cell-derived neuronal like cells. Silencing of Cttn reduced the numbers of neurites and growth cones, while pcDNA-Cttn exerted an opposite effect. The enhanced outgrowth of neurites by agomiR-124 can be reverted by co-treated si-Cttn. Finally, the interactions among miR-124-3p, IPO8, Ago1/2, and the Cttn promoter were verified in PC12 cells through RNA immunoprecipitation, RNA pull-down, and chromatin immunoprecipitation assays. Our results showed that miR-124-3p enhanced the function of neurons and promoted neurite outgrowth following SCI, at least partly by targeting the promoter of Cttn and activating its transcription. These findings elucidated the mechanism underlying the neuroprotective effects of miR-124-3p and revealed the therapeutic ability of the two molecules as targets associated with SCI.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8782-8795"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Potential Protective Effects of Intermittent Fasting Against Radiation-Induced Brain Damage in a Rat Model: Suggested Involvement of IRS-1/PI3 K/AKT and BDNF/TrkB Signaling Pathways. 间歇性禁食对大鼠辐射脑损伤的潜在保护作用：提示参与IRS-1/ pi3k /AKT和BDNF/TrkB信号通路

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-07-01 DOI: 10.1007/s12035-025-05059-1

Eman F S Taha, Hebatallah E Mohamed, Lobna M Anees, Hayam Mostafa, Eman S Eldin

{"title":"The Potential Protective Effects of Intermittent Fasting Against Radiation-Induced Brain Damage in a Rat Model: Suggested Involvement of IRS-1/PI3 K/AKT and BDNF/TrkB Signaling Pathways.","authors":"Eman F S Taha, Hebatallah E Mohamed, Lobna M Anees, Hayam Mostafa, Eman S Eldin","doi":"10.1007/s12035-025-05059-1","DOIUrl":"https://doi.org/10.1007/s12035-025-05059-1","url":null,"abstract":"Fasting has emerged as a promising therapeutic strategy for neurological disorders, offering protection against insults such as ionizing radiation (IR), which can cause irreversible brain damage. Intermittent fasting (IF), including alternate-day fasting (ADF) and time-restricted feeding (TRF), is being explored for its neuroprotective effects with potential involvement of key signaling pathways such as IRS-1/PI3K/AKT and BDNF/TrkB. Thirty-six male Wistar albino rats were randomly divided into six groups: normal feeding (NF, ad libitum feeding), ADF, TRF (6-h feeding window), NF plus radiation (NF-irradiated, 20-Gy cranial exposure), ADF plus radiation (ADF-irradiated), and TRF plus radiation (TRF-irradiated). Oxidative stress markers, antioxidant enzymes, liver and kidney function parameters, and gene/protein expression levels (IRS1, AKT1, PI3K, GFAP, 8-OHdG, BDNF, TrkB) were evaluated using enzyme-linked immunosorbent assay (ELISA) and RT-PCR, complemented by histopathological analysis. IR significantly impaired antioxidant defenses (GSH, GST, CAT), suppressed IRS-1/PI3K/AKT and BDNF/TrkB signaling, and elevated oxidative damage markers (MDA, ROS, 8-OHdG), inflammation (GFAP), and markers of organ dysfunction (ALT, AST, GGT, urea, creatinine). Both IF regimens mitigated these effects; however, TRF demonstrated greater efficacy than ADF. TRF more effectively reduced oxidative stress, improved antioxidant enzyme activity, and more robustly restored metabolic and neurotrophic signaling pathways. Both ADF and TRF provided neuroprotection against radiation-induced brain injury, but TRF exhibited superior outcomes in reducing oxidative stress and preserving neuronal integrity. These findings highlight TRF as a potentially more effective dietary strategy for mitigating radiation-induced neurotoxicity, with possible contributions from the modulation of IRS-1/PI3K/AKT and BDNF/TrkB pathways.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Re-Analyses of Samples From Amyotrophic Lateral Sclerosis Patients and Controls Identify Many Novel Small RNAs With Diagnostic And Prognostic Potential. 对肌萎缩侧索硬化症患者和对照组样本的重新分析发现了许多具有诊断和预后潜力的新型小rna。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-07-01 Epub Date: 2025-02-21 DOI: 10.1007/s12035-025-04747-2

Phillipe Loher, Eric Londin, Hristelina Ilieva, Piera Pasinelli, Isidore Rigoutsos

{"title":"Re-Analyses of Samples From Amyotrophic Lateral Sclerosis Patients and Controls Identify Many Novel Small RNAs With Diagnostic And Prognostic Potential.","authors":"Phillipe Loher, Eric Londin, Hristelina Ilieva, Piera Pasinelli, Isidore Rigoutsos","doi":"10.1007/s12035-025-04747-2","DOIUrl":"10.1007/s12035-025-04747-2","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease for which accurate diagnostic and prognostic biomarkers are needed. Toward this goal, we reanalyzed two published collections of datasets generated from the plasma and serum of ALS patients and controls. We profiled these datasets for isoforms of microRNAs (miRNAs) known as isomiRs, transfer RNA-derived fragments (tRFs), and ribosomal RNA-derived fragments (rRFs), placing all remaining reads into a group labeled \"not-itrs.\" We found that plasma and serum are rich in isomiRs (canonical, non-canonical, and non-templated), tRFs, rRFs, and members of an emerging class of small RNAs known as Y RNA-derived fragments (yRFs). In both analyzed collections, we found many isomiRs, tRFs, rRFs, and yRFs that are differentially abundant between patients and controls. We also performed a survival analysis that considered Riluzole treatment status, demographics (age at onset, age at enrollment, sex), and disease characteristics (ALSFRS, rD50, onset type) and found many of the differentially abundant small RNAs to be associated with survival time, with some of these associations being independent of Riluzole treatment. Unexpectedly, many not-itrs that did not map to the human genome mapped exactly to sequences from the SILVA database of ribosomal DNAs (rDNAs). Not-itrs from the plasma datasets mapped primarily to rDNAs from the order of Burkholderiales, and several of them were associated with patient survival. Not-itrs from the serum datasets also showed support for rDNA from Burkholderiales but a stronger support for rDNAs from the fungi group of the Nucletmycea taxon. The findings suggest that many previously unexplored small non-coding RNAs, including human isomiRs, tRFs, rRFs, and yRFs, could potentially serve as novel diagnostic and prognostic biomarkers for ALS.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8135-8149"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification and Validation of Biomarkers for Alzheimer's Disease Based on Akt and Wnt Signaling Pathways in Mouse Models. 基于Akt和Wnt信号通路的小鼠阿尔茨海默病生物标志物的鉴定和验证

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-07-01 Epub Date: 2025-02-24 DOI: 10.1007/s12035-025-04785-w

Ya-Han Wang, Hong-Yun Wu, Chao Xin, Kai-Xin Zhang, Ji-Wei Zhang, Hong-Wei Zhi

{"title":"Identification and Validation of Biomarkers for Alzheimer's Disease Based on Akt and Wnt Signaling Pathways in Mouse Models.","authors":"Ya-Han Wang, Hong-Yun Wu, Chao Xin, Kai-Xin Zhang, Ji-Wei Zhang, Hong-Wei Zhi","doi":"10.1007/s12035-025-04785-w","DOIUrl":"10.1007/s12035-025-04785-w","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disease that remains challenging to treat. Akt and Wnt play a role in complex cellular signaling, which is crucial for examining the onset of AD. In this study, we aimed to identify and analyze Akt pathway-related genes (ARGs) and Wnt pathway-related genes (WRGs) as AD biomarkers, determine the effects of ARGs and WRGs on AD, and verify these effects in AD mouse models. We searched for differentially expressed genes in the Gene Expression Omnibus database, constructed candidate gene protein-protein interaction networks, and used least absolute shrinkage and selection operator regression analysis and the support vector machine-recursive feature elimination algorithm to screen key genes. Correlation and functional similarity analyses of key genes, immune infiltration analysis, competing endogenous RNA network construction, and drug prediction of key genes were performed. Expression of key genes in streptozotocin-treated (STZ)-treated AD mice was validated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Bioinformatics analysis identified five key genes in AD: PRKACA, CDH3, ATP6V0C, DLL1, and CELSR2. Step-down tests, immunohistochemistry, and silver plate staining confirmed successful treatment of STZ-induced AD in mice. According to RT-qPCR analysis, the relative expression of DLL1 mRNA in AD mice was higher than that in control mice, whereas the relative expression of ATP6V0C and PRKACA mRNA in AD mice was lower than that in control mice; this was consistent with the results of bioinformatics analysis (p < 0.05). This study screened and validated AD biomarkers associated with the Akt and Wnt pathways in mouse models.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8279-8297"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomarker Profile in Peripheral Blood Cells Related to Alzheimer's Disease. 与阿尔茨海默病相关的外周血生物标志物谱。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-07-01 Epub Date: 2025-03-10 DOI: 10.1007/s12035-025-04767-y

Mirko Lomi, Filippo Geraci, Cristina Del Seppia, Cristina Dolciotti, Renata Del Carratore, Paolo Bongioanni

{"title":"Biomarker Profile in Peripheral Blood Cells Related to Alzheimer's Disease.","authors":"Mirko Lomi, Filippo Geraci, Cristina Del Seppia, Cristina Dolciotti, Renata Del Carratore, Paolo Bongioanni","doi":"10.1007/s12035-025-04767-y","DOIUrl":"10.1007/s12035-025-04767-y","url":null,"abstract":"In a healthy brain, neuroinflammation, controlled by the main intermediary for the immune response microglia and astrocytes, contributes to maintain physiological functions such as secretion of neurotrophic factors, removal of cell tau and amyloid-β (Aβ) debris, and local homeostasis. When the immune response becomes chronic, it can become pathological and fuel neuroinflammation, causing glial cells to malfunction and not perform their function of clearing debris, resulting in further damage to neurons. Multiple studies highlight that an intense crosstalk is activated between peripheral blood white cells (PBWCs) and central nervous system (CNS). Nevertheless, how PBWC can be carriers of biomarkers of the CNS neuropathological states it is still far to be completely known. In this work, we aimed to observe how PBWC content could be related to moderate-severity of DAT in order to have early signals from of pathological neurodegeneration brain initiate. Protein analysis have been performed in PBWC of Mild Cognitive Impairment (MCI) and DAT patients in respect to those of healthy controls and differently expressed proteins have been investigated. Our data showed a deregulation of pathways involved in neurodegeneration since from MCI level and deregulated proteins that can be considered markers for DAT onset and progression.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8949-8964"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biology, Pathology, and Targeted Therapy of Exosomal Cargoes in Parkinson's Disease: Advances and Challenges. 帕金森病外泌体装载物的生物学、病理学和靶向治疗：进展和挑战。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-07-01 Epub Date: 2025-02-25 DOI: 10.1007/s12035-025-04788-7

Faezeh Almasi, Faeze Abbasloo, Narges Soltani, Masoud Dehbozorgi, Atousa Moghadam Fard, Arash Kiani, Nasim Ghasemzadeh, Hassan Mesgari, Elaheh Zadeh Hosseingholi, Zahra Payandeh, Parjin Rahmanpour

{"title":"Biology, Pathology, and Targeted Therapy of Exosomal Cargoes in Parkinson's Disease: Advances and Challenges.","authors":"Faezeh Almasi, Faeze Abbasloo, Narges Soltani, Masoud Dehbozorgi, Atousa Moghadam Fard, Arash Kiani, Nasim Ghasemzadeh, Hassan Mesgari, Elaheh Zadeh Hosseingholi, Zahra Payandeh, Parjin Rahmanpour","doi":"10.1007/s12035-025-04788-7","DOIUrl":"10.1007/s12035-025-04788-7","url":null,"abstract":"Parkinson's disease (PD) involves the loss of dopamine neurons and accumulation of alpha-synuclein (α-syn), leading to Lewy bodies. While α-syn-targeting immunotherapies show promise, clinical application is challenging. Emerging strategies include nano-platforms for targeted delivery and imaging, and cell-based therapies with patient-specific dopaminergic neurons, aiming to enhance treatment effectiveness despite challenges. Exosome-based methodologies are emerging as a promising area of research in PD due to their role in the spread of α-syn pathology. Exosomes are small extracellular vesicles that can carry misfolded α-syn and transfer it between cells, contributing to the progression of PD. They can be isolated from biological fluids such as blood and cerebrospinal fluid, making them valuable biomarkers for the disease. Additionally, engineering exosomes to deliver therapeutic agents, including small molecules, RNA, or proteins, offers a novel approach for targeted therapy, capitalizing on their natural ability to cross the blood-brain barrier (BBB). Ongoing studies are evaluating the safety and efficacy of these engineered exosomes in clinical settings. This review explores the role of exosomes in PD, focusing on their potential for diagnosis, treatment, and understanding of pathology. It highlights advancements and future directions in using exosomes as biomarkers and therapeutic tools.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8381-8399"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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