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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

Neuroinflammation as a therapeutic target in Huntington's disease

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Neural Regeneration Research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani H.Palpagama Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： Huntington inflammation medicine

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

Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural Regeneration Research 2025年第2期20卷 475-476页

作者： Jackson Powell Tobias Steinschaden Rose Horowitz Yuanquan Song Raymond G.Perelman Center for Cellular and molecular therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate Group University of PennsylvaniaPhiladelphiaPAUSA Department of Pathology and Laboratory medicine University of PennsylvaniaPhiladelphiaPAUSA Medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural *** intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following *** the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to *** works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of *** role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

Neurodegenerative diseases:a hotbed for splicing defects and the potential therapies

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Translational Neurodegeneration 2021年第2期10卷 195-212页

作者： Dunhui Li Craig Stewart McIntosh Frank Louis Mastaglia Steve Donald Wilton May Thandar Aung-Htut centre for molecular medicine and innovative therapeutics Health Futures InstituteMurdoch UniversityPerthWestern AustraliaAustralia Perron Institute for Neurological and Translational Science Centre for Neuromuscular and Neurological DisordersThe University of Western AustraliaPerthWestern AustraliaAustralia

Precursor messenger RNA(pre-mRNA)splicing is a fundamental step in eukaryotic gene expression that systematically removes non-coding regions(introns)and ligates coding regions(exons)into a continuous message(mature mRNA).This process is highly regulated and can be highly flexible through a process known as alternative splicing,which allows for several transcripts to arise from a single gene,thereby greatly increasing genetic plasticity and the diversity of *** splicing is particularly prevalent in neuronal cells,where the splicing patterns are continuously changing to maintain cellular homeostasis and promote neurogenesis,migration and synaptic *** continuous changes in splicing patterns and a high demand on many cis-and trans-splicing factors contribute to the susceptibility of neuronal tissues to splicing *** resultant neurodegenerative diseases are a large group of disorders defined by a gradual loss of neurons and a progressive impairment in neuronal *** of the most common neurodegenerative diseases involve some form of splicing defect(s),such as Alzheimer’s disease,Parkinson’s disease and spinal muscular *** growing understanding of RNA splicing has led to the explosion of research in the field of splice-switching antisense oligonucleotide *** we review our current understanding of the effects alternative splicing has on neuronal differentiation,neuronal migration,synaptic maturation and regulation,as well as the impact on neurodegenerative *** will also review the current landscape of splice-switching antisense oligonucleotides as a therapeutic strategy for a number of common neurodegenerative disorders.

关键词： Neurodegenerative diseases Parkinson’s disease Alzheimer’s disease Alternative splicing Splicing defects Antisense oligonucleotides Splice-switching Disease-modifying treatment

Surface-Engineered Li4Ti5O12 Nanostructures for High-Power Li-Ion Batteries

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Nano-Micro Letters 2020年第2期12卷 235-245页

作者： Binitha Gangaja Shantikumar Nair Dhamodaran Santhanagopalan centre for Nanosciences and molecular medicine Amrita Vishwa Vidyapeetham

Materials with high-power charge–discharge capabilities are of interest to overcome the power limitations of conventional Li-ion *** this study,a unique solvothermal synthesis of Li4Ti5O12 nanoparticles is proposed by using an off-stoichiometric precursor ratio.A Li-deficient off-stoichiometry leads to the coexistence of phaseseparated crystalline nanoparticles of Li4Ti5O12 and TiO2 exhibiting reasonable high-rate ***,after the solvothermal process,an extended aging of the hydrolyzed solution leads to the formation of a Li4Ti5O12 nanoplate-like structure with a self-assembled disordered surface layer without crystalline *** Li4Ti5O12 nanoplates with the disordered surface layer deliver ultrahighrate performances for both charging and discharging in the range of 50–300C and reversible capacities of 156 and 113 mAh g−1 at these two rates,***,the electrode exhibits an ultrahigh-charging-rate capability up to 1200C(60 mAh g−1;discharge limited to 100C).Unlike previously reported high-rate half cells,we demonstrate a high-power Li-ion battery by coupling Li4Ti5O12 with a high-rate LiMn2O4 *** full cell exhibits ultrafast charging/discharging for 140 and 12 s while retaining 97 and 66% of the anode theoretical capacity,***-(25℃),low-(−10℃),and high-(55℃)temperature cycling data show the wide temperature operation range of the cell at a high rate of 100C.

关键词： Ultrafast charging Li-ion battery Lithium titanate Off-stoichiometric synthesis Surface chemistry

Humanized mice are susceptible to Salmonella typhi infection

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Cellular & molecular Immunology 2011年第1期8卷 83-87页

作者： M Firoz Mian Elisabeth A Pek Meghan J Chenoweth Ali A Ashkar Institute for Infectious Disease Research Centre for Gene TherapeuticsDepartment of Pathology and Molecular MedicineMcMaster UniversityHamiltonOntarioCanada

Salmonella enterica serovar Typhi is a pathogen that only infects ***,there is no animal model for studying this ***,alymphoid RAG2^(-/-)/γc^(-/-) mice engrafted with human leukocytes,known as humanized mice,have been successfully utilized to develop experimental models for several human-specific viral infections,including HIV,human-like dengue fever and hepatitis C *** is known about the usefulness and feasibility of the humanized mouse model for the study of human-specific bacterial pathogens,such as *** aim of this study was to determine if Salmonella enterica serovar Typhi could establish productive infection in humanized *** we report that intravenous inoculation of *** into humanized mice,but not controls,established *** *** bacterial loads were found in the liver,spleen,blood and bone marrow of mice reconstituted with human leukocytes,but not in the unreconstituted control ***,***-infected humanized mice lost significant body weight,and some of the infected mice displayed neurological *** data suggest,for the first time,that humanized mice are susceptible to *** challenge and that this model can be utilized to study the pathogenesis of *** develop novel therapeutic strategies.

关键词： animal model humanized mice RAG2-/-γc-/- Salmonella typhi

The role of sequestosome 1/p62 protein in amyotrophic lateral sclerosis and frontotemporal dementia pathogenesis

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Neural Regeneration Research 2020年第12期15卷 2186-2194页

作者： Adriana Delice Foster Sarah Lyn Rea Harry Perkins Institute of Medical Research University of Western Australia Perron Institute for Neurological and Translational Science Centre for Neuromuscular and Neurological DisordersThe University of Western AustraliaNedlandsWestern AustraliaAustralia centre for molecular medicine and innovative therapeutics Murdoch University Murdoch Western Australia Australia

Amyotrophic lateral sclerosis and frontotemporal lobar degeneration are multifaceted diseases with genotypic,pathological and clinical *** such overlap is the presence of SQSTM1/p62 *** traditionally mutations manifesting in the ubiquitin-associated domain of p62 were associated with Paget’s disease of bone,mutations affecting all functional domains of p62 have now been identified in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients.p62 is a multifunctional protein that facilitates protein degradation through autophagy and the ubiquitin-proteasome system,and also regulates cell survival via the Nrf2 antioxidant response pathway,the nuclear factor-kappa B signaling pathway and *** in these signaling and protein degradation pathways have been observed in amyotrophic lateral sclerosis and frontotemporal lobar degeneration,and mutations that affect the role of p62 in these pathways may contribute to disease *** this review we discuss the role of p62 in these pathways,the effects of p62 mutations and the effect of mutations in the p62 modulator TANK-binding kinase 1,in relation to amyotrophic lateral sclerosis-frontotemporal lobar degeneration pathogenesis.

关键词： aggregate/inclusion body formation amyotrophic lateral sclerosis-frontotemporal lobar degeneration autophagy cell signaling mitophagy p62/SQSTM1 protein degradation

Dissecting the cell microenvironment of ovarian endometrioma through single-cell RNA sequencing

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Science China Life Sciences 2025年第1期68卷 116-129页

作者： Jiangpeng Wu Siyu Xia Wenting Ye Yan Sun Jing Cai Fubing Yu Haiping Wen Xiuwei Yi Taikang Li Mingwei Chen Jiayun Chen Ge Song Chuanbin Yang Yali Song Jigang Wang Department of Reproductive medicine Dongguan Maternal and Child Health Care Hospital Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalSouthern University of Science and Technology State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Reproductive medicine Center Foshan Women and Children Hospital State Key Laboratory of Antiviral Drugs School of PharmacyHenan University

Ovarian endometrioma（OE）, also known as “chocolate cysts,” is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+and KLF2+epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies.

关键词： ovary high-throughput sequencing transcriptomics gene expression analysis ligand-receptor analysis