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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural regeneration research 2025年第3期20卷 725-739页

作者： Benjamin r.Helmold Angela Ahrens Zachary Fitzgerald p.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SpAST spastin

Heterogeneity of mature oligodendrocytes in the central nervous system

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Neural regeneration research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam M.r.Groh Moein Yaqubi Qiao-Ling Cui Jo Anne Stratton G.r.Wayne Moore Jack p.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to *** the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by robertson and río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature ***,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination ***,modern molecular investigations,employing techniques such as single cell/nucleus rNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined *** studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte *** research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

Emerging potential of progranulin-dependent SorCS2 signaling in healthy and diseased nervous systems

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Neural regeneration research 2025年第9期20卷 2591-2593页

作者： Alena Salasova Anders Nykjær Danish research Institute of Translational Neuroscience DANDrITE-Nordic EMBL partnership for Molecular Medicine and Centre of Excellence PROMEMODepartment of BiomedicineAarhus UniversityAarhusDenmark

The formation of the mammalian nervous system and its maturation into sensory,motor,cognitive,and behavioral circuits is a complex process that begins during early embryogenesis and lasts until young *** neurodevelopm... 详细信息

关键词： progr jointly CS2

Antisense oligonucleotides provide optimism to the therapeutic landscape for tauopathies

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Neural regeneration research 2025年第3期20卷 803-804页

作者： Glenn A.Harris Lauren r.Hirschfeld rainwater Charitable Foundation Fort WorthTXUSA

Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MApT) and can be classified as either 3-repeat(3r) or 4-repeat(4r) based on the number of repeat domains from alternative splicing of exon 10 of the MApT gene.

关键词： tau metabolism diseases

Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

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Neural regeneration research 2025年第6期20卷 1707-1708页

作者： Siva S.V.p.Sakamuri Anil Sakamuri Department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and Department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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Neural regeneration research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

In silico analysis of lncrNA-mirNA-mrNA signatures related to Sorafenib effectiveness in liver cancer cells

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World Journal of Gastroenterology 2025年第3期31卷 84-102页

作者： patricia de la Cruz-Ojeda Ester parras-Martínez raquel rey-pérez Jordi Muntané Functional Genomics of Solid Tumors Laboratory Centre de Recherche des CordeliersParis 75006France Department of Oncology Surgery Cell Therapy and Organ TransplantationInstitute of Biomedicine of SevilleVirgen del Rocio University HospitalSeville 41013Spain Biomedical research Center for Hepatic and Digestive Diseases CIBERehdMadrid 28029Spain Department of Medical physiology and Biophysics University of SevilleSeville 41009Spain

BACKGrOUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology *** is still a recommended treatment for a large proportion of patients with advanced *** patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 *** To define the long non-codingrNA-microrNA-mrNA(lncrNA-mirNA-mrNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in rNAseq studies using Sorafenib-treated HepG2 and SNU449 *** available software analyses allowed us to establish the lncrNA-mirNA-mrNA regulatory axes following treatment in HepG2 and SNU449 *** HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 *** rNA,including small and long rNA,was extracted with a commercial mirNeasy *** was carried out for the identification of changes in lncrNA-mirNA-mrNA regulatory *** MALAT,THAp9-AS1 and SNGH17 appeared to coordinately regulate mir-374b-3p and mir-769-5p that led to upregulation of SMAD7,TIrArp,TFAp4 and FAXDC2 in HepG2 ***12,EpB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,mir-195-5p and VEGFA in SNU449 *** axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAp4 were of high relevance for Sorafenib response in HepG2 cells,whereas pVT1/hsa-mir-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib *** Critical lncrNAs acting as sponges of mirNA were identified that regulated mrNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIrArp,TFAp4,FAXDC2 and ADrB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.

关键词： Cell culture Hepatocellular carcinoma Non-coding rNA rNAseq Sorafenib

Machine learning applications in healthcare clinical practice and research

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World Journal of Clinical Cases 2025年第1期13卷 16-21页

作者： Nikolaos-Achilleas Arkoudis Stavros p papadakos research Unit of radiology and Medical Imaging School of MedicineNational and Kapodistrian University of AthensAthens 11528Greece 2^(nd)Department of radiology “Attikon”General University HospitalMedical SchoolNational and Kapodistrian University of AthensChaidari 12462Greece Department of Gastroenterology Laiko General HospitalNational and Kapodistrian University of AthensAthens 11527Greece

Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human *** its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and *** this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical *** authors of this study conducted an analysis using both multiple linear regression(MLr)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and *** addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+***,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLr),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.

关键词： Machine Learning Artificial Intelligence Clinical practice research Glomerular filtration rate Non-alcoholic fatty liver disease Medicine

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