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Neural Regeneration Research 2024年第3期19卷 619-628页

作者： Jun Chang Yujiao Li Xiaoqian shan Xi Chen Xuhe Yan Jianwei Liu Lan Zhao First Teaching Hospital of Tianjin University of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina Tianjin University of Traditional Chinese Medicine TianjinChina

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with alzheimer’s ***,promoting neuroplasticity may represent an effective strategy with which alzheimer’s disease can be *** to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to *** events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian ***,neural stem cells are considered to represent a potential regenerative therapy with which to improve alzheimer’s disease and other neurodegenerative *** this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating alzheimer’s disease in the clinic.

关键词： alzheimer’s disease amyloid-β cell therapy extracellular vesicle neural stem cell synaptic plasticity tau

Unveiling DNA methylation in alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro Joana Figueiro-silva Neurodegenerative diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of alzheimer’s disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular Life science University of ZurichZurichSwitzerland

The intricacies of alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA *** review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in alzheimer’s disease *** examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and alzheimer’s disease *** entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the ***,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal ***,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory *** complex role of BIN1 in late-onset alzheimer’s disease is underscored by its association with altered methylation *** the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and alzheimer’s disease *** research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying alzheimer’s disease progression.

关键词： alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

Environmental enrichment in combination with Bifidobacterium breve HNXY26M4 intervention amplifies neuroprotective benefits in a mouse model of alzheimer's disease by modulating glutamine metabolism of the gut microbiome

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Food science and Human Wellness 2024年第2期13卷 982-992页

作者： Guangsu Zhu Min Guo Jianxin Zhao Hao Zhang Gang Wang Wei Chen state Key Laboratory of Food science and Resources Jiangnan UniversityWuxi 214122China school of Food science and Technology Jiangnan UniversityWuxi 214122China (Yangzhou)Institute of Food Biotechnology Jiangnan UniversityYangzhou 225004China National Engineering Center of Functional Food Jiangnan UniversityWuxi 214122China

The gut microbiota-brain axis has emerged as a novel target for alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive ***,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive ***,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)*** this study,we found that compared with EE or *** treatment alone,*** intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic ***,using microbiome and metabolome profiling,we found that the combination of *** and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite ***,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain ***,combined *** intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut *** findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.

关键词： alzheimer’s disease Bifidobacterium breve Environmental enrichment Glutamine metabolism Microbiota-gut-brain axis

An Assisted Diagnosis of alzheimer’s disease Incorporating Attention Mechanisms Med-3D Transfer Modeling

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Computers, Materials & Continua 2024年第1期78卷 713-733页

作者： Yanmei Li Jinghong Tang Weiwu Ding Jian Luo Naveed Ahmad Rajesh Kumar school of Artificial Intelligence Chongqing University of TechnologyChongqing400054China Computer school China West Normal UniversityNanchong637009China Department of Computer science Prince Sultan UniversityRiyadh11586Saudi Arabia Yangtze Delta Region Institute(Huzhou) University of Electronic Science and Technology of ChinaHuzhou313001China

alzheimer’s disease(AD)is a complex,progressive neurodegenerative *** subtle and insidious onset of its pathogenesis makes early detection of a formidable challenge in both contemporary neuroscience and clinical *** this study,we introduce an advanced diagnostic methodology rooted in theMed-3D transfermodel and enhanced with an attention *** aim to improve the precision of AD diagnosis and facilitate its early ***,we employ a spatial normalization technique to address challenges like clarity degradation and unsaturation,which are commonly observed in imaging ***,an attention mechanism is incorporated to selectively focus on the salient features within the imaging *** upon this foundation,we present the novelMed-3D transfermodel,designed to further elucidate and amplify the intricate features associated *** proposedmodel has demonstrated promising results,achieving a classification accuracy of 92%.To emphasize the robustness and practicality of our approach,we introduce an adaptive‘hot-updating’auxiliary diagnostic *** system not only enables continuous model training and optimization but also provides a dynamic platform to meet the real-time diagnostic and therapeutic demands of AD.

关键词： alzheimer’s disease channel attention Med-3D hot update

Activation of autophagy by Citri Reticulatae semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2467-2479页

作者： Yong Tang Jing Wei Xiao-Fang Wang Tao Long Xiaohong Xiang Liqun Qu Xingxia Wang Chonglin Yu Xingli Xiao Xueyuan Hu Jing Zeng Qin Xu Anguo Wu Jianming Wu Dalian Qin Xiaogang Zhou Betty Yuen-Kwan Law Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao Special Administrative RegionChina sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity screening and Druggability Evaluation for Chinese Materia Medica Southwest Medical UniversityLuzhouSichuan ProvinceChina Eye school and Key Laboratory of sichuan Province Ophthalmopathy Prevention&Cure and Visual Function Protection of Chengdu University of TCM ChengduSichuan ProvinceChina school of Basic Medical sciences Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Ophthalmology The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Neurology The First People’s Hospital of NeijiangNeijiangSichuan ProvinceChina

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in alzheimer’s *** Reticulatae semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae semen on alzheimer’s disease remains *** the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae semen extract on amyloid-beta-induced apoptosis in PC12 cells were first *** Reticulatae semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of *** addition,Citri Reticulatae semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo ***,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae semen extract was *** importantly,Citri Reticulatae semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg alzheimer’s disease *** revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae semen extract is a potential natural therapeutic agent for alzheimer’s disease via its neuroprotective autophagic effects.

关键词： alzheimer’s disease amyloid-beta apoptosis autophagy Caenorhabditis elegans Citri Reticulatae semen

NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2400-2410页

作者： Bo Hu Jiaping Zhang Jie Huang Bairu Luo Xiansi Zeng Jinjing Jia Department of Pathology and Municipal Key-Innovative Discipline of Molecular Diagnostics Jiaxing Hospital of Traditional Chinese MedicineJiaxing UniversityJiaxingZhejiang ProvinceChina Research Center of Neuroscience Jiaxing University Medical CollegeJiaxingZhejiang ProvinceChina Department of Clinical Pathology Jiaxing University Master Degree Cultivation BaseZhejiang Chinese Medical UniversityJiaxingZhejiang ProvinceChina

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell *** is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of alzheimer’s *** this review,we summarize the possible pathogenic mechanisms of alzheimer’s disease,focusing on *** also describe the structures of NLRP3 and NLRP1 and the role their activation plays in alzheimer’s ***,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for alzheimer’s disease.

关键词： alzheimer’s disease caspase-1 GsDMD inflammasome neuroinflammation NLRP1 NLRP3 pyroptosis therapeutic strategies

Monoclonal antibodies and aptamers:The future therapeutics for alzheimer’s disease

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Acta Pharmaceutica sinica B 2024年第7期14卷 2795-2814页

作者： Alvaro Barrera-Ocampo Facultad de Ingenierıa Diseno y Ciencias AplicadasDepartamento de Ciencias Farmaceuticas y QuimicasGrupo NaturaUniversidad IcesiCali 760031Colombia

alzheimer’s disease(AD)is considered the most common and prevalent form of dementia of adult-onset with characteristic progressive impairment in cognition and *** cure for AD has not been found yet and the treatments available until recently were only *** of multidisciplinary approaches and efforts made by pharmaceutical companies,it was only in the past two years that new drugs were approved for the treatment of the *** beta(Ab)immunotherapy is at the core of this therapy,which is one of the most innovative approaches looking to change the course of *** technology is based on synthetic peptides or monoclonal antibodies(mAb)to reduce Ab levels in the brain and slow down the advance of ***,this article reviews the state of the art about AD neuropathogenesis,the traditional pharmacologic treatment,as well as the modern active and passive immunization describing approved drugs,and drug prototypes currently under investigation in different clinical *** addition,future perspectives on immunotherapeutic strategies for AD and the rise of the aptamer technology as a non-immunogenic alternative to curb the disease progression are discussed.

关键词： Ab Monoclonal antibody DNA aptamers Cognitive impairment alzheimer’s disease Clinical trials Immunotherapy Machine learning

Intermittent Theta Burst stimulation Attenuates Cognitive Deficits and alzheimer’s disease-Type Pathologies via IsCA1-Mediated Mitochondrial Modulation in APP/Ps1 Mice

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Neuroscience Bulletin 2024年第2期40卷 182-200页

作者： Yang Zhu Hao Huang Zhi Chen Yong Tao Ling-Yi Liao shi-Hao Gao Yan-Jiang Wang Chang-Yue Gao Department of Rehabilitation Medicine Daping HospitalArmy Medical UniversityChongqing 400042China Department of Neurology and Center for Clinical Neuroscience Daping HospitalArmy Medical UniversityChongqing 400042China Department of special Medicine Daping HospitalArmy Medical UniversityChongqing 400042China

Intermittent theta burst stimulation(iTBs),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with alzheimer’s disease(AD).However,the specific mechanism underlying iTBs-induced cognitive enhancement remains *** studies suggested that mitochondrial functions are modulated by magnetic ***,we showed that iTBs upregulates the expression of iron-sulfur cluster assembly 1(IsCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/Ps1 *** vivo and in vitro studies revealed that iTBs modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ***,iTBs rescues cognitive decline and attenuates AD-type pathologies in APP/Ps1 *** present study uncovers a novel mechanism by which iTBs modulates mitochondrial respiration and function via IsCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in *** provide the mechanistic target of iTBs that warrants its therapeutic potential for AD patients.

关键词： Intermittent theta burst stimulation alzheimer’s disease Iron-sulfur cluster assembly 1 Mitochondrial dysfunction Neurodegeneration

Neuroprotective effect of liraglutide and memantine in a rat model of alzheimer’s disease

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Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 207-214页

作者： Duaa M.Bakhshwin Foziya W.Alhalabi Mohamad Omar Barasheed Ahmed M.Bakhshwin Maha H.Jamal Mohammed A.Bazuhair Fatemah O.Kamel Rania M.Magadmi Zoheir A Damanhouri samar M.Alsaggaf Department of Clinical Pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia Hera General Hospital MakkahSaudi Arabia Department of Pathology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia Department of Clinical Anatomy Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia

Objective:To assess the effect of memantine combined with liraglutide on aluminum chloride(AlCl_(3))and D-galactose(D-GAL)-induced neurotoxicity in ***:Male Wistar rats were divided into 5 groups of 5 animals each:the positive control,the negative control,the memantine-treated group,the liraglutide-treated group,and the combination group treated with memantine and ***_(3)and D-GAL were used to induce *** tests,brain beta-amyloid protein,and oxidative stress biomarkers were ***:The Morris water maze test indicated an enhanced memory in the combination ***,the combination treatment of liraglutide and memantine resulted in a remarkable reduction in the beta-amyloid protein level in the brain *** inflammation and oxidative stress biomarkers were significantly reduced,and the levels of antioxidant parameters were ***:The combination of liraglutide and memantine exerts neuroprotective effects and enhances memory and cognitive functions in rats with alzheimer’s disease.

关键词： alzheimer’s disease Cognitive function Glucagonlike peptide-1 Liraglutide Memantine

Exploring the vital role of microglial membrane receptors in alzheimer’s disease pathogenesis: a comprehensive review

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BIOCELL 2024年第7期48卷 1011-1022页

作者： JUN-FENG ZHAO YI-RAN JIANG TIAN-LIN GUO YONG-QING JIAO XUN WANG Department of Neurointervention Center Dalian No.3 People’s HospitalDalian Medical UniversityDalianChina Department of Clinical Medicine China Medical UniversityShenyangChina

Neurodegenerative diseases constitute a broad category of diseases caused by the degeneration of the *** are mainly manifested by the gradual loss of neuron structure and function and eventually can cause death or loss of *** the global population ages rapidly,increased people are being diagnosed with neurodegenerative *** has been established that the onset of alzheimer’s disease(AD)is closely linked with increasing age and its major pathological features include amyloid-beta plaques(Aβ),Tau hyperphosphorylation,Neuroﬁbrillary tangles(NFTs),neuronal death as well as synaptic *** involvement of microglia is crucial in the pathogenesis and progression of AD and exhibits a dual *** instance,in the early stage of AD,microglia surface membrane proteins or receptors can participate in immunophagocytosis,and anti-inﬂammatory functions and act as a physical barrier after recognizing various ligands such as Aβand ***,in the later stage of the disease,membrane receptors on the surface of microglia can cause its activation to release a substantial quantity of pro-inﬂammatory *** can amplify the neuroinﬂammatory *** rapid decline of normal immune phagocytosis can result in the continuous accumulation of abnormal proteins,leading to neuronal dysfunction and destruction of the formed physical barrier as well as the neurovascular *** can also increase the transformation of microglia from anti-inﬂammatory phenotype M2 to pro-inﬂammatory phenotype M1,induce severe neuronal injury or apoptosis,and aggravate the progression of *** to few articles have focused on the AD-related membrane protein receptors on microglia,thus in this paper,we have reviewed several representative microglial membrane proteins or receptors about their speciﬁc roles and functions implicated in AD,and expect that there will be more in-depth research and scientiﬁc research results in the treatment of AD by targeted regulation of mi

关键词： Neurodegeneration Glial cell Receptor alzheimer’s disease