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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

Therapeutic potential of exercise-hormone irisin in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1555-1564页

作者： Eunhee Kim Rudolph ETanzi Se Hoon Choi Genetics and Aging Research Unit MassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMAUSA McCance Center for Brain health Massachusetts General HospitalBostonMAUSA

Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.

关键词： Alzheimer's disease exercise fibronectin typeⅢdomain-containing protein 5(FNDC5) irisin

Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2538-2555页

作者： Jie Jin Huajing Zhang Qianying Lu Linqiang Tian Sanqiao Yao Feng Lai Yangfan Liang Chuanchuan Liu Yujia Lu Sijia Tian Yanmei Zhao Wenjie Ren Institute of Disaster and Emergency Medicine Tianjin UniversityTianjinChina Key Laboratory for Disaster Medicine Technology TianjinChina Henan Medical Key Laboratory for Research of Trauma and Orthopedics The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan ProvinceChina Clinical Medical Center of Tissue Engineering and Regeneration Xinxiang Medical UniversityXinxiangHenan ProvinceChina Institutes of health Central Plain Xinxiang Medical UniversityXinxiangHenan ProvinceChina School of Public health Xinxiang Medical UniversityXinxiangHenan ProvinceChina

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future *** principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular tar

关键词： blood-brain barrier cognitive dysfunction exosomes gene silencing immunotherapy inorganic nanomaterials liposome nanoparticles neuroinflammation polymer nanoparticles stem cells

The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases BeijingChina Key Laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

Glia-to-neuron reprogramming to the rescue?

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Neural Regeneration Research 2025年第5期20卷 1395-1396页

作者： Jack W.Hickmott Cindi M.Morshead Department of Surgery University of TorontoTorontoONCanada Donnelly Centre for Cellular and Biomolecular Research TorontoONCanada Institute of Biomedical Engineering University of TorontoTorontoONCanada The KITE Research Institute Toronto Rehabilitation InstituteUniversity Health NetworkTorontoONCanada

Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative *** brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be *** exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.

关键词： programming passing proof

Dietary carbohydrate intake and risk of type 2 diabetes:a 16-year prospective cohort study

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Science China Life Sciences 2025年

作者： Lu Gan Yi Yang Bin Zhao Kai Yu Kehua Guo Fang Fang Zhiguang Zhou Demetrius Albanes Jiaqi Huang Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University CSU-Sinocare Research Center for Nutrition and Metabolic Health Xiangya School of Public Health Central South UniversityFurong Laboratory Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Department of Health and Human Services School of Computer Science and Engineering Central South University Institute of Environmental Medicine Karolinska Institute National Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University

Despite considerable research underscoring the importance of carbohydrate intake in relation to the risk of type 2 diabetes(T2D), a comprehensive assessment of this relationship is currently lacking. We aimed to examine the associations of various types and food sources of dietary carbohydrate intake with the risk of T2D, to evaluate potential effect modification by other factors, including genetic susceptibility,and to explore the potential mediators for such associations. The present study included 161,872 participants of the UK Biobank who were free of prevalent cancer, cardiovascular disease, or diabetes, and had at least one validated 24-h dietary recall assessment. Multivariableadjusted age-stratified Cox proportional hazard regression models were applied to estimate hazard ratios(HRs) and 95% confidence intervals(CI) for the associations of various types and food sources of dietary carbohydrate intake with risk of T2D. During a median follow-up of13.6 years, 4,176 incident cases of T2D were identified. In the multivariable-adjusted models, a greater intake of fiber, carbohydrates from whole grains, and carbohydrates from non-starchy vegetables was significantly associated with a lower risk of T2D(highest vs. lowest quantile, HR [95% CI]=0.70 [0.62–0.79], 0.74 [0.67–0.82], and 0.83 [0.75–0.92], respectively, all P for trend <0.005). In contrast, a higher intake of starch and carbohydrate from starchy vegetables was associated with an increased risk of T2D(highest vs. lowest quantile, HR [95%CI]=1.31 [1.16–1.48] and 1.19 [1.09–1.31], respectively, both P for trend <0.005). Replacing one serving of refined grains or starchy vegetables with an equal amount of whole grains or non-starchy vegetables was associated with 4% to 10% lower risk of T2D(all P values <0.001).The observed associations were generally similar across population subgroups, including individuals with different genetic susceptibility to T2D. Mediation analyses of the inverse association between T

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Combinatorial therapies for spinal cord injury repair

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Neural Regeneration Research 2025年第5期20卷 1293-1308页

作者： Carla S.Sousa Andreia Monteiro António J.Salgado Nuno A.Silva Life and health Sciences Research Institute(ICVS) School of MedicineUniversity of MinhoCampus de Gualtar-gualtarBragaPortugal ICVS/3B’s Associate Lab PT Government Associated LabCampus de Gualtar-gualtarBragaPortugal

Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

关键词： electric stimulation neural tissue regeneration neuroprotection polytherapy spinal cord injury

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child health Hospital) FuzhouFujian ProvinceChina Medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

New insights on the role of chondroitin sulfate proteoglycans in neural stem cell–mediated repair in spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1699-1700页

作者： Seyed Mojtaba Hosseini Soheila Karimi-Abdolrezaee Department of Physiology and Pathophysiology Spinal Cord Research CentreRady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada Manitoba Multiple Sclerosis Research Center WinnipegMBCanada Children Hospital Research Institute of Manitoba WinnipegMBCanada

Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord undergoes a cascade of secondary injury mechanisms that are driven by disruption of the blood-spinal cord ba rrier,vascula r inju ry,glial reactivity,neu roinfla mmation,oxidative stress,lipid peroxidation,and glutamate excitotoxicity that culminate in neuronal and oligodendroglial cell death,demyelination,and axonal damage(Alizadeh et al.,2019).To achieve a meaningful functional recovery after SCI,regeneration of new neurons and oligodendrocytes and their successful growth and integration within the neural network are critical steps for reconstructing the damaged spinal cord tissue (Fischer et al.,2020).

关键词： peroxidation Fischer injury