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Searching for new drugs to treat Alzheimer’s disease dementia through multiple pathways

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World Journal of Clinical Cases 2025年第1期13卷 22-28页

作者： Hua Bai Xiao-Feng Feng Department of Neurology The Third Affiliated Hospital of Guizhou Medical UniversityDuyun 558099Guizhou ProvinceChina Department of Neurology Wulong Branch of the People's Hospital Affiliated to Chongqing UniversityWulong 408500ChongqingChina Department of Neurology Guizhou Medical UniversityGuiyang 550004Guizhou ProvinceChina

Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic *** treatment of dementia mainly includes symptomatic treatment by controlling the primary disease and accompanying symptoms,nutritional support therapy for repairing nerve cells,psychological auxiliary treatment,and treatment that improves cognitive function through *** them,drug therapy to improve cognitive function is *** review focuses on introducing and commenting on some recent progress in exploring drugs to improve cognitive function,especially the new progress in drug treatment for *** mainly discuss the opportunities and challenges in finding and developing new therapeutic drugs from the aspects of acetylcholinesterase,N-methyl-D-aspartate glutamate receptor,amyloid protein,tau protein and chronic immune inflammation.

关键词： Alzheimer's disease Dementia Cholinesterase inhibitor Beta amyloid Tau protein

Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

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Neural Regeneration Research 2025年第11期20卷 3193-3206页

作者： Ling-Xiao Yi Hui Ren Woon Genevieve Saw Li Zeng Eng King Tan Zhi Dong Zhou National Neuroscience Institute Singapore Nanyang Technology university Singapore Department of Neurology Singapore General HospitalSingapore Signature Research Program in Neuroscience and Behavioral Disorders Duke-NUS Medical SchoolSingapore

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative *** the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and *** induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease *** current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem *** benefits of induced pluripotent stem cell-based research are *** dopaminergic neuron differentiation protocols from induced pluripotent stem cells are *** emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are ***,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

关键词： dopaminergic neurons induced pluripotent stem cells Parkinson's disease stem cell approaches

Iron-handling solute carrier SLC22A17 as a blood-brain barrier target after stroke

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Neural Regeneration Research 2025年第11期20卷 3207-3208页

作者： Xueqi Ren Wenlu Li Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Neuroprotection Research Laboratories Departments of Radiology and NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

The pathophysiology of ischemic stroke is complex and multifactorial,involving various forms of cell death such as apoptosis,autophagy,and necrosis.A recent study suggests that oxidative and inflammatory stress can induce ferroptosis,a specialized form of cell death characterized by the accumulation of lipid peroxides dependent on intracellular iron overload(Li and Jia,2023).

关键词： death specialized barrier

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration Research 2025年第4期20卷 917-935页

作者： Dian Jiao Lai Xu Zhen Gu Hua Yan Dingding Shen Xiaosong Gu Academy of medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated hospital of Nantong university NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological *** regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of *** pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota *** results are lacking for conventional treatments for *** resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with ***-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research *** review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of *** also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current *** studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic ***,many new technologies for the diagnosis and treatment of epilepsy are being ***,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

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Neural Regeneration Research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang Department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Neurosurgery Surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira S.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

Movement analysis in the diagnosis and management of Parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 485-486页

作者： Johannes Burtscher Nicolas Bourdillon Jules MJanssen Daalen Aurélien Patoz Julien FBally Martin Kopp Davide Malatesta Bastiaan RBloem Institute of Sport Sciences University of LausanneLausanneSwitzerland Radboud university medical Center Department of NeurologyDonders Institute for BrainCognition and BehaviorCenter of Expertise for Parkinson and Movement DisordersNijmegenThe Netherlands Radboud university medical Center Department of Medical BioSciencesNijmegenThe Netherlands Research and Development Department Volodalen Swiss Sport LabAigleSwitzerland Service of Neurology Department of Clinical NeurosciencesLausanne University Hospital(CHUV)and University of Lausanne(UNIL)LausanneSwitzerland Department of Sport Science University of InnsbruckInnsbruckAustria

Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall ***,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses *** biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).

关键词： diagnosis Clinical eventually

Netrin-1 signaling pathway mechanisms in neurodegenerative diseases

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Neural Regeneration Research 2025年第4期20卷 960-972页

作者： Kedong Zhu Hualong Wang Keqiang Ye Guiqin Chen Zhaohui Zhang Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Neurology The First Hospital of Hebei Medical UniversityBrain Aging and Cognitive Neuroscience Laboratory of Heibei ProvinceShijiazhuangHebei ProvinceChina Faculty of Life and Health Sciences Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal *** profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic *** amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of *** findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative *** a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.

关键词： Alzheimer’s disease axon guidance colorectal cancer Netrin-1 receptors Netrin-1 signaling pathways Netrin-1 neurodegenerative diseases neuron survival Parkinson’s disease UNC5C

Tilting homeostatic and dyshomeostatic microglial balance in health and disease:transforming growth factor-beta1 as a critical protagonist

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Neural Regeneration Research 2025年第10期20卷 2895-2897页

作者： Nicolas Hugues Yu Luo Department of Molecular and Cellular Biosciences University of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program University of CincinnatiCincinnatiOHUSA Division of Immunobiology Cincinnati Children’s Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOHUSA

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the *** the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).

关键词： Figure signature critical