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Exploiting fly models to investigate rare human neurological disorders

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Neural Regeneration research 2025年第1期20卷 21-28页

作者： Tomomi Tanaka Hyung-Lok Chung department of Neurology Houston Methodist Research InstituteHoustonTXUSA department of Neurology Weill Cornell Medical CollegeNew YorkNYUSA

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological *** attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted *** investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary *** tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological *** boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug *** can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical *** this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic *** discuss rare diseases associated with both neuron-expressed and glial-expressed *** cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal *** we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell ***-of-fun

关键词： ACOX1 Drosophila melanogaster glia lipid metabolism model organisms neuroinflammation neurologic disorders neuron rare disease VLCFA

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration

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Neural Regeneration research 2025年第10期20卷 2741-2757页

作者： Qianzi Jin Suyu Wang Yujia Yao Qin Jiang Keran Li department of Ophthalmology The Affiliated Eye Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina The Fourth School of clinical Medicine Nanjing Medical UniversityNanjingJiangsu ProvinceChina

Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts ***,the specific pathogenesis remains unclear,and effective early treatment options are consequently *** microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a *** intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other *** dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many *** recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the ***,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s ***,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular ***,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable *** such,the intestinal flora may play an important role in age-related macular *** the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic ***,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular ***-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the inte

关键词： age-related macular degeneration biological agents blinding eye disease dietary nutrition fecal microbial transplantation gut-eye axis intestinal flora metabolite microecology neurodegenerative disease

EZH2-dependent myelination following sciatic nerve injury

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Neural Regeneration research 2025年第8期20卷 2382-2394页

作者： Hui Zhu Li Mu Xi Xu Tianyi Huang Ying Wang Siyuan Xu Yiting Wang Wencong Wang Zhiping Wang Hongkui Wang Chengbin Xue research Center of clinical Medicine Affiliated Hospital of Nantong UniversityKey Laboratory of Neuroregeneration of Jiangsu and Ministry of EducationCo-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina Medical School of Nantong University NantongJiangsu ProvinceChina department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina department of Rehabilitation Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina department of Critical Care Medicine Nantong Fourth People’s HospitalNantongJiangsu ProvinceChina

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve ***,the gene regulatory network of regenerated myelin differs from that of native *** of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in *** further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were *** results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain *** highlights the crucial role of Ezh2 in initiating Schwann cell ***,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type *** suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and *** conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve *** EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

关键词： demyelination EZH2 myelination peripheral nerve injury PRC2 remyelination Schwann cells sciatic nerve crush sciatic nerve transection

Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

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Neural Regeneration research 2025年第5期20卷 1258-1276页

作者： Qing Qiu Mengting Yang Danfeng Gong Haiying Liang Tingting Chen department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Jiangsu Province Key Laboratory of Inflammation and Molecular drug Target NantongJiangsu ProvinceChina department of Pharmacy Longyan First Affiliated Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be u

关键词： astrocytes calcium channels central nervous system extracellular ion concentration microglia neurological disorders neurons potassium channels

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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Neural Regeneration research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu Dan Liu department of Pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang clinical Precision Medicine research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and Transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

Maximizing biomass utilization: An integrated strategy for coproducing multiple chemicals

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Journal of Energy Chemistry 2025年第1期100卷 180-191页

作者： Byeongchan Ahn Sua Jo Jonggeol Na J.Jay Liu Young-Ju Kim Wangyun Won department of Chemical and Biological Engineering Korea University department of Chemical Engineering (Integrated process) Kyung Hee University department of Chemical Engineering and Materials Science Ewha Womans University department of Chemical Engineering Pukyong National University Resources Engineering Plant research department Korea Institute of Geoscience and Mineral Resources

Lignocellulosic biomass is one of the viable solutions to alleviate the global warming. However, the limited utilization of biomass majorly focused on cellulose and hemicellulose restricts the economic and environmental feasibilities. To cope with this issue, we proposed an integrated process of co-producing 1,6-hexanediol（1,6-HDO） with tetrahydrofuran and adipic acid from biomass, referred to as Strategy A. To compare the impacts of lignin upgrading and feedstock, Strategy B, which co-produces tetrahydrofuran alone, and Strategy C, which is the traditional route to produce 1,6-HDO from fossil fuels, were used. Heat networks are also designed to reduce operating costs and indirect carbon emissions due to energy consumption, saving 87% and 83% of the heat and cooling requirements, respectively, in Strategy A. The market competitiveness of Strategy A was evaluated by determining the minimum selling price through techno-economic analysis, and sustainability was thoroughly investigated by quantifying the environmental impacts through both midpoint and endpoint life-cycle assessments（LCAs）.Strategy A was found to be the most favorable both economically（USRDSCHARDOLLAR3,402/ton） and environmentally（-26.9 kg CO2eq.）. This indicates that lignin valorization is not only economically but also environmentally preferred. Finally, changes in economic and environmental feasibilities depending on economic, process, and environmental parameters were investigated using sensitivity and uncertainty analyses. The results of these analyses provide valuable insight into bio-based chemical production.

关键词： Carbon capture and utilization

Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National clinical research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

Role of metabolic dysfunction and inflammation along the liver-brain axis in animal models with obesity-induced neurodegeneration

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Neural Regeneration research 2025年第4期20卷 1069-1076页

作者： Evridiki Asimakidou Eka Norfaishanty Saipuljumri Chih Hung Lo Jialiu Zeng department of clinical Neurosciences University of CambridgeCambridgeUK School of Applied Science Republic PolytechnicSingaporeSingapore Lee Kong Chian School of Medicine Nanyang Technological UniversitySingaporeSingapore

The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s ***-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this *** lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory *** and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting *** insulin resistance further exacerbates brain insulin resistance and *** interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal ***,translating these findings to clinical practice requires further investigation into human *** conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and *** these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.

关键词： Alzheimer’s disease inflammatory cytokines insulin resistance lipid