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Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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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

Surfing the nano-wave:Emerging trends in cancer diagnostics and therapy

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Nano Research 2025年第1期18卷 520-544页

作者： Genping Fu Yuting Weng Yunfan Li Carl Ho Yiyu Fu Wenxuan Wang Songbin Fu Wenjing Sun Jie Lin Xiaoyu Fan Binbin Jia Mengdi Cai Linlin Li laboratory of Medical genetics Harbin Medical UniversityHarbin 150081China Key laboratory of Preservation of human genetics Resources and Disease Control in China(Harbin Medical University) Ministry of EducationHarbin 150081China Beijing Key laboratory for Optical Materials and Photonic Devices Department of ChemistryCapital Normal UniversityBeijing 100048China College of Materials and Chemical Engineering Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion MaterialsChina Three Gorges UniversityYichang 443002China Washington University School of Medicine in St.Louis St.LouisMO 63110USA Ningbo Institute of Materials Technology and Engineering Chinese Academy of SciencesNingbo 315201China Aix-Marseille College Wuhan University of TechnologyWuhan 430070China

Facing the growing global challenge posed by cancer,the quest for more accurate and potent cancer diagnostic and therapeutic strategies continues to require a multidisciplinary integration *** review firstly summarizes various types of nanoparticles in cancer ***,it offers a comprehensive overview of signalenhancing techniques for visualizing in situ tumors,along with multimodal diagnostic methods for detecting *** for tumor therapy,cutting-edge drug delivery methods that can cross biological barriers and the pinpoint targeting of tumor lesions for precise medical intervention are *** the domain of therapeutic diagnostics,we elucidate the theoretical underpinnings and structural paradigms that underlie a spectrum of advanced diagnostic and therapeutic ***,we present a compendium of publications delineating the clinical applications of each nano-based theragnostic integration ***,this comprehensive review discusses the safety concerns pertaining to the clinical application of nanoparticles and proposes some strategic recommendations to enhance the precision and safety of theragnostic-guided,nanotechnology-based clinical practices.A deeper understanding of nanomaterials,together with intimate interdisciplinary collaborations,nano-wave will most probably guide human beings to win the battle against cancers.

关键词： nanoparticles drug delivery gastric cancer glioma glioblastoma

Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

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Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： Yanting Liu Wei Huang Jiayi Wen Xin Xiong Ting Xu Qi Wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili Yang Guangdong Key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal ***,it remains largely unclear how PINK1 and Parkin are expressed in mammalian *** has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small *** this issue is critical for elucidating the in vivo roles of PINK1 and ***,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate *** the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate *** found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey ***1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable *** double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial *** findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution

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

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

Towards Understanding RNA-Mediated Neurological Disorders

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Journal of genetics and Genomics 2014年第9期41卷 473-484页

作者： Ranhui Duan Sumeet Sharma Qiuping Xia Kathryn Garber Peng Jin State Key laboratory of Medical genetics Central South University Department of human genetics Emory University School of Medicine

RNA-mediated mechanisms of disease pathogenesis in neurological disorders have been recognized in the context of certain repeat expansion disorders. This RNA-initiated neurodegeneration may play a more pervasive role in disease pathology beyond the classic dynamic mutation disorders. Here, we review the mechanisms of RNA toxicity and aberrant RNA processing that have been implicated in ageing-related neurological disorders. We focus on diseases with aberrant sequestration of RNA-binding proteins, bi-directional tran- scription, aberrant translation of repeat expansion RNA transcripts （repeat-associated non-ATG （RAN） translation）, and the formation of pathological RNA：DNA secondary structure （R-loop）. It is likely that repeat expansion disorders arise from common mechanisms caused by the repeat expansion mutations. However, the context of the repeat expansion determines the specific molecular consequences, leading to clinically distinct disorders.

关键词： Neurodegeneration Repeat expansion RNA toxicity RAN translation R-loop

Irreversible electroporation for metastatic pancreatic carcinoma with liver metastasis:What does the evidence say

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World Journal of Clinical Cases 2025年第3期13卷 30-34页

作者： Ranit Seal Akash Bararia Bitan Kumar Chattopadhyay Nilabja Sikdar Department of General Surgery IPGME&R and SSKM HospitalKolkata 700020West BengalIndia human genetics Unit Indian Statistical InstituteKolkata 700108West BengalIndia Estaurine and Coastal Studies Foundation Howrah 711101India

Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some ***,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy *** studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.

关键词： Irreversible electroporation Locally advanced pancreatic carcinoma Metastatic pancreatic carcinoma Advanced pancreatic carcinoma Chemotherapy

Association of WNK1 exon 1 polymorphisms with essential hypertension in Hani and Yi minorities of China

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Journal of genetics and Genomics 2011年第4期38卷 165-171页

作者： Yina Cun Jin Li Wenru Tang Xiaozhi Sheng Haijing Yu Bingrong Zheng Chunjie Xiao laboratory for Conservation and Utilization of Bio-resources and human genetics Center of Yunnan UniversityKunming 650091China

The association of polymorphisms in exon 1 of the WNK1 gene with essential hypertension in the minority groups of Hani and Yi of China was investigated in the case-control *** sequence of 1257 bp containing the WNK1 gene exon 1 was determined in 1307 individuals（649 essential hypertension subjects and 658 controls）to identify SNPs in Hani and Yi minority *** of eleven previously known SNPs （rs3168640,rs11885,rs11554421 and rs34880640）were *** SNP analysis indicated that SNPs rs11885 and rs11554421 were significantly associated with hypertension in both Hani and Yi populations,and rs34880640 was significantly associated with hypertension in Hani but not in Yi population,adjusted for *** analysis indicated that the haplotype H1 significantly decreased the risk of hypertension in both *** results suggested that WNK1 polymorphisms were involved in the predisposition of essential hypertension in Hani and Yi populations and its effects showed a clear population *** finding supported the importance of population specificity in determining the genetic factors associated with diseases and thus disease treatment.

关键词： WNK1 SNPs Haplotype Essential hypertension Hani population Yi population

Expression of the human TSPY gene in the brains of transgenic mice suggests a potential role of this Y chromosome gene in neural functions

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Journal of genetics and Genomics 2011年第5期38卷 181-191页

作者： Tatsuo Kido Stephanie Schubert Jrg Schmidtke Yun-Fai Chris Lau Division of Cell and Developmental genetics Department of MedicineVA Medical Centerand Institute for Human GeneticsUniversity of California Institute of human genetics Hannover Medical School

The testis specific protein Y-encoded （TSPY） is a member of TSPY/SET/NAP1 superfamily, encoded within the gonadoblastoma locus on the Y chromosome. TSPY shares a highly conserved SET/NAP-domain responsible for protein--protein interaction among TSPY/SET/NAP 1 proteins. Accumulating data, so far, support the role of TSPYas the gonadoblastoma gene, involved in germ cell tumorigenesis. The X-chromosome homolog of TSPY, TSPX is expressed in various tissues at both fetal and adult stages, including the brain, and is capable of interacting with the multi-domain adapter protein CASK, thereby influencing the synaptic and transcriptional functions and developmental regulation of CASK in the brain and other neural tissues. Similar to TSPX, we demonstrated that TSPY could interact with CASK at its SET/NAP-domain in cultured cells. Transgenic mice harboring a human TSPYgene and flanking sequences showed specific expression of the human TSPYtransgene in both testis and brain. The neural expression pattern of the human TSPYgene overlapped with those of the endogenous mouse Cask and Tspx gene. Similarly with TSPX, TSPY was co-localized with CASK in neuronal axon fibers in the brain, suggesting a potential role（s） of TSPY in development and/or physiology of the nervous system.

关键词： TSPY TSPX CASK Y chromosome Neuron Testis