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Neural Regeneration Research 2025年第5期20卷 1407-1408页

作者： Daniel Adam Felix Langerscheidt Hans Zempel Institute of human genetics University Hospital CologneCologneGermany Center for molecular Medicine Cologne(CMMC) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

Dip2a regulates stress susceptibility in the basolateral amygdala

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Neural Regeneration Research 2025年第6期20卷 1735-1748页

作者： Jing Li Zixuan He Weitai Chai Meng Tian Huali Yu Xiaoxiao He Xiaojuan Zhu Key laboratory of molecular Epigenetics Ministry of Education Institute of Genetics and CytologyNortheast Normal UniversityChangchunJilin ProvinceChina

Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

关键词： 5-hydroxytryptamine acute restraint stress basolateral amygdala CaMKII neurons DIP2A metabolomics neurotransmitters principal component analysis stress susceptibility tryptophan

Genetic and epigenetic alterations associated with gestational diabetes mellitus and adverse neonatal outcomes

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World Journal of Clinical Pediatrics 2025年第1期14卷 6-20页

作者： Amreen Shamsad Tanu Gautam Renu Singh Monisha Banerjee molecular and human genetics laboratory Department of ZoologyUniversity of LucknowLucknow 226007Uttar PradeshIndia Department of Obstetrics and Gynecology King George’s Medical UniversityLucknow 226003Uttar PradeshIndia

Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of *** is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological *** investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to *** alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic *** between genes and environment,resulting in differ-ential gene expression patterns may lead to *** suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and *** modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in *** is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well *** present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal *** addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.

关键词： Gene expression Gestational diabetes mellitus Feto-maternal outcome Epigenetic alteration molecular biomarkers

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel Institute of human genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

New glucocerebrosidase antibodies can advance research in the field of neurodegenerative disorders

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Neural Regeneration Research 2025年第4期20卷 1085-1086页

作者： Charis Ma Krystyna Rytel Yu Chen Ellen Sidransky Medical genetics Branch National Human Genome Research InstituteNational Institutes of HealthBethesdaMDUSA

In medical research,there are times when the introduction of a new tool can launch scientific discovery in new *** antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)research,the dearth of validated antibodies for different applications has impeded progress in studies of disease pathogenesis and therapeutic *** recent introduction of new,rigorously evaluated antibodies can now propel research into the link between glucocerebrosidase and Parkinson’s disease(PD)as well as aspects of the pathobiology of Gaucher disease(Jong et al.,2024).

关键词： antibodies cerebro

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

Therapeutic potential of berberine against neurodegenerative diseases

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Science China(Life Sciences) 2015年第6期58卷 564-569页

作者： JIANG WenXiao LI ShiHua LI XiaoJiang Department of Microbiology and molecular genetics Emory University Department of human genetics Emory University

Berberine(BBR) is an organic small molecule isolated from various plants that have been used in traditional Chinese medicine. Isolation of this compound was its induction into modern medicine, and its usefulness became quickly apparent as seen in its ability to combat bacterial diarrhea, type 2 diabetes, hypercholesterolemia, inflammation, heart diseases, and more. However, BBR's effects on neurodegenerative diseases remained relatively unexplored until its ability to stunt Alzheimer's disease(AD) progression was characterized. In this review, we will delve into the multi-faceted defensive capabilities and bio-molecular pathways of BBR against AD, Parkinson's disease(PD), and trauma-induced neurodegeneration. The multiple effects of BBR, some of which enhance neuro-protective factors/pathways and others counteract targets that induce neurodegeneration, suggest that there are many more branches to the diverse capabilities of BBR that have yet to be uncovered. The promising results seen provide a convincing and substantial basis to support further scientific exploration and development of the therapeutic potential of BBR against neurodegenerative diseases.

关键词： Huntington's disease berberine autophagy protein aggregation

Interplay of SOX transcription factors and microRNAs in the brain under physiological and pathological conditions

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Neural Regeneration Research 2022年第11期17卷 2325-2334页

作者： Milena Stevanovic Danijela Stanisavljevic Ninkovic Marija Mojsin Danijela Drakulic Marija Schwirtlich laboratory for human molecular genetics Institute of Molecular Genetics and Genetic EngineeringUniversity of BelgradeBelgradeSerbia University of Belgrade Faculty of BiologyBelgradeSerbia Serbian Academy of Sciences and Arts BelgradeSerbia

Precise tuning of gene expression,accomplished by regulato ry networks of transcription factors,epigenetic modifiers,and microRNAs,is crucial for the proper neural development and function of the brain *** SOX transcription factors are involved in regulating diverse cellular processes during embryonic and adult neurogenesis,such as maintaining the cell stemness,cell prolife ration,cell fate decisions,and terminal diffe rentiation into neurons and glial *** represent a class of small non-coding RNAs that play important roles in the regulation of gene *** with other gene regulatory factors,microRNAs regulate different processes during neurogenesis and orchestrate the spatial and temporal expression important for *** emerging data point to a complex regulatory network between SOX transcription factors and microRNAs that govern distinct cellular activities in the developing and adult *** SOX/mic roRNA interplay in signaling pathways that influence the homeostasis and plasticity in the brain has been revealed in various brain pathologies,including neurodegenerative disorders,traumatic brain injury,and *** strategies that target SOX/microRNA interplay have emerged in recent years as a promising tool to target neural tissue regeneration and enhance neuro restoration.N umerous studies have confirmed complex intera ctions between microRNAs and SOX-specific mRNAs regulating key features of *** in mind the crucial roles of SOX genes and microRNAs in neural development,we focus this review on SOX/microRNAs interplay in the brain during development and adulthood in physiological and pathological *** focus was made on their interplay in brain pathologies to summarize current knowledge and highlight potential future development of molecular therapies.

关键词： dysregulation of miRNA expression glioblastoma gliogenesis glioma stem cells ischemic stroke neural stem cells neural tissue regeneration neurodegenerative diseases neurodevelopment neurogenesis SOX/miRNA interplay traumatic brain injury

Effective Isolation of Retrotransposons and Repetitive DNA Families from the Wheat Genome

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Journal of Integrative Plant Biology 2010年第7期52卷 679-691页

作者： Motonori Tomita Munenori Asao Aya Kuraki molecular genetics laboratory Faculty of AgricultureTottori University

New classes of repetitive DNA elements were effectively identified by isolating small fragments of the elements from the wheat genome. A wheat A genome library was constructed from Triticum monococcum by degenerate cleavage with EcoO1091, the recognition sites of which consisted of 5＇-PuGGNCCPy-3＇ multi-sequences. Three novel repetitive sequences pTm6, pTm69 and pTm58 derived from the A genome were screened and tested for high copy number using a blotting approach, pTm6 showed identity with integrase domains of the barley Tyl-Copia-retrotransposon BARE-1 and pTm58 showed similarity to the barley Ty3-gypsy-like retrotransposon Romani. pTm69, however, constituted a tandem array with useful genomic specificities, but did not share any identity with known repetitive elements. This study also sought to isolate wheat D-genome-specific repetitive elements regardless of the level of methylation, by genomic subtraction. Total genomic DNA of Aegilops tauschii was cleaved into short fragments with a methylation-insensitive 4 bp cutter, Mbol, and then common DNA sequences between Ae. tauschii and Triticum turgidum were subtracted by annealing with excess T. turgidum genomic DNA. The D genome repetitive sequence pAt1 was isolated and used to identify an additional novel repetitive sequence family from wheat bacterial artificial chromosomes with a size range of 1 395-1 850 bp. The methods successfully led pathfinding of two unique repetitive families.

关键词： DNA Effective Isolation of Retrotransposons and Repetitive DNA Families from the Wheat Genome AABB

Construction of the Seed-Coat cDNA Microarray and Screening of Differentially Expressed Genes in Barley

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Acta Biochimica et Biophysica Sinica 2004年第10期36卷 695-700页

作者： Jin-Song PANG*, Meng-Yuan HE, and Bao LIU laboratory of molecular Epigenetics, Institute of genetics and Cytology, Northeast Normal University, Changchun 130024, China laboratory of molecular Epigenetics Institute of Genetics and Cytology Northeast Normal University

Some barley mutants can synthesize neither anthocyanins nor proanthocyanidins in the seed coat, which is related to several genes in locus Ant13, but the exact model of action remains unknown. We used the cDNA microarray technology with barley transcription-deficient mutant (ant13-152) that does not synthesize proanthocyanidins as the tester, and its wild type genotype (Triumph) as the driver, to study this question. Six-thousand and forty-eight clones from the wild type Morex testa+pericarp cDNA library were amplified using PCR, and the DNA fragments were spotted on commercial amino-modified glass slide as microarray. The mRNAs from the developing seed coat (8–15 days) of both the mutant and the wild-type barley plants were isolated, and labeled respectively with Cy3-dUTP and Cy5-dUTP when reversely trans- cribed to cDNAs. The labeled cDNAs were used as probes, mixed at the same molar concentration, and hybridized with the DNA fragments on the slide. Seventy clones exhibiting marked differential expression (ratio>4) were identified from the microarray. All the 25 cDNA clones that showed an over-expression in wild type in comparison to the mutant ant13-152 were sequenced. It was found that most of these over- expressing clones were transcription/translation and hordein-associated genes. These results have laid a solid material basis for further elucidation of the metabolic pathway in proanthocyanidin synthesis in barley and likely other plants.

关键词： barley seed coat proanthocyanidin cDNA microarray