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Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

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Neural Regeneration Research 2025年第3期20卷 695-714页

作者： Beibei Wu Yuqing Liu Hongli Li Lemei Zhu Lingfeng Zeng Zhen Zhang Weijun Peng department of Integrated Traditional Chinese&Western Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina Yangsheng College of Traditional Chinese Medicine Guizhou University of Traditional Chinese MedicineGuiyangGuizhou ProvinceChina Qinhuangdao Shanhaiguan Pharmaceutical Co. LtdQinhuangdaoHebei ProvinceChina National Clinical Research Center for Mental Disorder The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary *** amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease *** abnormalities are commonly observed in patients with Alzheimer's *** liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's ***,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's *** this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol ***,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

关键词： ABCA1 Alzheimer's disease amyloid-beta apolipoprotein E cholesterol metabolism liver liver X receptor low-density lipoprotein receptor-related protein 1 peripheral clearance tauroursodeoxycholic acid

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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

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Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin Jiannan Wu Junqiang Yan department of neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology Laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu Yu Wang Hanlin Huang Jun Ke Feng Chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina The second department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang John Marshall department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA department of neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

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Neural Regeneration Research 2025年第5期20卷 1350-1363页

作者： Hui Li Laurent Seugnet department of neurology Xijing HospitalXi’anShaanxi ProvinceChina Centre de Recherche en Neurosciences de Lyon Integrated Physiology of the Brain Arousal Systems(WAKING)UniversitéClaude Bernard Lyon 1INSERM U1028CNRS UMR 5292BronFrance

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular *** the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other *** these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral *** the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of ***-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared *** their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy ***,they impact GABAergic neurons and the excitation/inhibition *** rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock *** mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully *** sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory *** mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these *** this context,the Drosophila model,though underutilized,holds promise in shedding new light on these *** findings indicate its po

关键词： branched-chain amino acids cardiovascular health circadian clock drosophila insulin metabolism sleep γ-aminobutyric acid

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Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi Pradeepkiran Priyanka Rawat Arubala P.Reddy Erika Orlov PHemachandra Reddy department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA department of Pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA department of neurology Texas Tech University Health Sciences CenterLubbockTXUSA department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA department of Public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

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Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

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Neural Regeneration Research 2017年第9期12卷 1551-1558页

作者： Yan Zou Wei-feng Zhang Hai-ying Liu Xia Li Xing Zhang Xiao-fang Ma Yang Sun Shi-yi Jiang Quan-hong Ma De-en Xu department of neurology The Second People's Hospital of Wuxi

The contactin-associated protein （Caspr） family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family- CNTNAP1 （Casprl）, CNTNAP2 （Caspr2）, CNTNAP3 （Caspr3）, CNTNAP4 （Caspr4） and CNTNAP5 （Caspr5）, Casprl-5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Casprl participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.

关键词： nerve regeneration contactin-associated protein family myelinated axon structure function Alzheimer's disease multiple sclerosis autism spectrum disorders neurodegeneration neural regeneration

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New exploration on pathogenesis and early diagnosis of gestational diabetes

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World Journal of Clinical Cases 2025年第1期13卷 1-5页

作者： Hua Bai department of neurology The Third Affiliated Hospital of Guizhou Medical UniversityDuyun 558099Guizhou ProvinceChina

Gestational diabetes mellitus(GDM)refers to varying degrees of abnormal glucose metabolism that occur during pregnancy and excludes patients pre-viously diagnosed with *** is a unique among the four subtypes of diabetes classified by the international World Health Organization *** GDM patients constitute a small proportion of the total number of diabetes cases,the incidence of GDM has risen significantly over the past decade,posing substantial risk to pregnant women and ***,it warrants considerable *** pathogenesis of GDM is generally considered to resemble that of type II diabetes,though it may have distinct *** blood biochemical proteins in the context of GDM can help elucidate its pathogenesis,thereby facilitating more effective prevention and management *** article reviews this critical clinical issue to enhance the medical community's sufficient understanding of GDM.

关键词： Gestational diabetes mellitus Pathogenesis Proteomics RBP4 ANGPTL8

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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

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miR-15b-5p targeting amyloid precursor protein is involved in the anti-amyloid eflect of curcumin in swAPP695-HEK293 cells

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Neural Regeneration Research 2019年第9期14卷 1603-1609页

作者： Hong-Ying Liu Xian Fu You-Fu Li Xian-Liang Li Zhen-Yu Ma Ying Zhang Qing-Chun Gao department of neurology the Second Affiliated Hospital of Guangzhou Medical University

Curcumin exerts a neuroprotective effect on Alzheimer’s disease;however,it is not known whether microRNAs are involved in this protective *** study was conducted using swAPP695-HEK293 cells as an Alzheimer’s disease cell ***695-HEK293 cells were treated with 0,0.5,1,2,5,and 10μM curcumin for 24 *** changes in miR-15b-5p,miR-19a-3p,miR-195-5p,miR-101-3p,miR-216b-5p,miR-16-5p and miR-185-5p expression were assessed by real-time quantitative polymerase chain *** mRNA and protein levels of amyloid precursor protein,amyloid-β40 and amyloid-β42 were evaluated by quantitative real-time polymerase chain reaction,western blot assays and enzyme-linked immunosorbent ***695-HEK293 cells were transfected with miR-15b-5p mimic,or treated with 1μM curcumin 24 hours before miR-15b-5p inhibitor *** effects of curcumin on amyloid precursor protein,amyloid-β40 and amyloid-β42 levels were evaluated by western blot assays and enzyme-linked immunosorbent *** assays were used to analyze the interaction between miR-15b-5p and the 3′-untranslated region of amyloid precursor *** results show that amyloid precursor protein and amyloid-βexpression were enhanced in swAPP695-HEK293 cells compared with HEK293 parental *** suppressed the expression of amyloid precursor protein and amyloid-βand up-regulated the expression of miR-15b-5p in swAPP695-HEK293 *** addition,we found a negative association of miR-15b-5p expression with amyloid precursor protein and amyloid-βlevels in the curcumin-treated *** assays revealed that miR-15b-5p impaired the luciferase activity of the plasmid harboring the 3′-untranslated region of amyloid precursor *** findings indicate that curcumin down-regulates the expression of amyloid precursor protein and amyloid-βin swAPP695-HEK293 cells,which was partially mediated by miR-15b-5p via targeting of the 3′-untranslated region of amyloid precursor protein.

关键词： nerve regeneration Alzheimer’s disease natural plant drug curcuminoids miRNAs amyloid precursor protein amyloid-β 3′-untranslated region Luciferase assays neurons neural regeneration

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