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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

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

Die in pieces:How Drosophila sheds light on neurite degeneration and clearance

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Journal of genetics and Genomics 2019年第4期46卷 187-199页

作者： Maria L.Sapar Chun Han Weill Institute for Cell and molecular biology Department of Molecular Biology and GeneticsCornell University

Dendrites and axons are delicate neuronal membrane extensions that undergo degeneration after physical injuries. In neurodegenerative diseases, they often degenerate prior to neuronal death. Understanding the mechanisms of neurite degeneration has been an intense focus of neurobiology research in the last two decades. As a result, many discoveries have been made in the molecular pathways that lead to neurite degeneration and the cell-cell interactions responsible for the subsequent clearance of neuronal debris. Drosophila melanogaster has served as a prime in vivo model system for identifying and characterizing the key molecular players in neurite degeneration, thanks to its genetic tractability and easy access to its nervous system. The knowledge learned in the fly provided targets and fuel for studies in other model systems that have further enhanced our understanding of neurodegeneration. In this review, we will introduce the experimental systems developed in Drosophila to investigate injuryinduced neurite degeneration, and then discuss the biological pathways that drive degeneration. We will also cover what is known about the mechanisms of how phagocytes recognize and clear degenerating neurites, and how recent findings in this area enhance our understanding of neurodegenerative disease pathology.

关键词： Drosophila Neurite degeneration Axon Dendrite Wallerian degeneration Phagocyte Phagocytosis PS exposure Injury assay

Memories of Ray Wu by a Colleague

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Science China(Life Sciences) 2009年第2期52卷 133-134页

作者：杨碧瓘 molecular biology & genetics at Cornell University

I first met Ray Wu in the spring of 1977 during my inter-view at Cornell where he was the Chair of the Section of Biochemistry, molecular and Cell biology. The meeting was brief and unremarkable but it achieved what it was meant to achieve. After I joined the Section of BMCB at Cornell as assistant professor that fall, I soon appreciated that

关键词：邓小平杨振宁李政道钱三强四化科举

Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： Antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

Matrix metalloproteinase gene expressions might be oxidative stress targets in gastric cancer cell lines

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Chinese Journal of Cancer Research 2013年第3期25卷 322-333页

作者： Salih Gencer Anil Cebeci Meliha Burcu Irmak-Yazicioglu Department of genetics and Bioengineering Faculty of Engineering Fatih University Department of molecular biology and genetics Faculty of Engineering and Natural Sciences Uskudar University Department of molecular biology and genetics Faculty of Arts and Sciences Halic University

Oxidative stress is linked to increased risk of gastric cancer and matrix metalloproteinases （MMPs） are important in the invasion and metastasis of gastric cancer. We aimed to analyze the effect of the accumulation of oxidative stress in the gastric cancer MKN-45 and 23132/87 cells following hydrogen peroxide （H202） exposure on the expression patterns of MMP-1, MMP-3, MMP-7, MMP-9, MMP-10, MMP- 1 1, MMP- 12, MMP-14, MMP- 15, MMP- 17, MMP-23, MMP-28, and β-catenin genes. Methods： The mRNA transcripts in the cells were determined by RT-PCR. Following H202 exposure, oxidative stress in the viable cells was analyzed by 2＇,7＇-dichlorofluorescein diaeetate （DCFH-DA）. Caffeie acid phenethyl ester （CAPE） was used to eliminate oxidative stress and the consequence of H2O2 exposure and its removal on the expressions of the genes were evaluated by quantitative real-time PCR. Results： The expressions of MMP-1, MMP-7, MMP-14, MMP-15, MMP-17 and β-catenin in MKN-45 cells and only the expression of MMP-15 in 23132/87 cells were increased. Removal of the oxidative stress resulted in decrease in the expressions of MMP genes of which the expressions were increased after H202 exposure. β-catenin, a transcription factor for many genes including MMPs, also displayed decreased levels of expression in both of the cell lines following CAPE treatment. Conclusions： Our data suggest that there is a remarkable link between the accumulation of oxidative stress and the increased expressions of MMP genes in the gastric cancer cells and MMPs should be considered as potential targets of therapy in gastric cancers due to its continuous exposure to oxidative stress.

关键词： Oxidative stress hydrogen peroxide (H202) matrix metalloproteinases (MMPs) expression eaffeicacid phenethyl ester (CAPE)

Novel Insights from Live-imaging in Shoot Meristem Development

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Journal of Integrative Plant biology 2010年第4期52卷 393-399页

作者： Paja Sijacic Department of Cell biology and molecular genetics University of MarylandCollege Park

Microscopic imaging of fluorescent reporters for key meristem regulators in live tissues is emerging as a powerful technique, enabling researchers to observe dynamic spatial and temporal distribution of hormonal and developmental regulators in living cells. Aided by time-lapse microphotography, new types of imaging acquisition and analysis software, and computational modeling, we are gaining significant insights into shoot apical meristem （SAM） behavior and function. This review is focused on summarizing recent advances in the understanding of SAM organization, development, and behavior derived from live-imaging techniques. This includes the revelation of mechanical forces in microtubule-controlled anisotropic growth, the role of the CLV-WUS network in the specification of peripheral zone and central zone cells, the multiple feedback loops involving cytokinin in controlling WUS expression, auxin dynamics in determining the position of new primordia, and, finally, sequence of regulatory events leading to de novo assembly of shoots from callus in culture. Future studies toward formulating ＂digital SAM＂ that incorporates multi-dimensional data ranging from images of SAM morphogenesis to a genome-scale expression map of SAM will greatly enhance our ability to understand, predict, and manipulate SAM, containing the stem cells that give rise to all above ground parts of a plant.

关键词： Novel Insights from Live-imaging in Shoot Meristem Development

Lipidomics as a Principal Tool for Advancing Biomedical Research

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Journal of genetics and Genomics 2013年第8期40卷 375-390页

作者： Sin Man Lam Guanghou Shui State Key Laboratory of molecular Developmental biology Institute of Genetics and Developmental BiologyChinese Academy of Sciences

Lipidomics, which targets at the construction of a comprehensive map of lipidome comprising the entire lipid pool within a cell or tissue, is currently emerging as an independent discipline at the interface of lipid biology, technology and medicine. The diversity and complexity of the biological lipidomes call for technical innovation and improvement to meet the needs of various biomedical studies. The recent wave of expansion in the field of lipidomic research is mainly attributed to advances in analytical technologies, in particular, the development of new mass spectrometric and chromatographic tools for the characterization and quantification of the wide array of diverse lipid species in the cellular lipidome. Here, we review some of the key technical advances in lipidome analysis and put forth the applications of lipidomics in addressing the biological roles of lipids in numerous disease models including the metabolic syndrome, neurodegenerative diseases and infectious diseases, as well as the increasing urgency to construct the lipidome inventory for various mammalian/organism models useful for biomedical research.

关键词： Lipidomics Mass spectrometry Metabolic syndrome Neurodegenerative diseases Infectious diseases

RLKs orchestrate the signaling in plant male-female interaction

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Science China(Life Sciences) 2016年第9期59卷 867-877页

作者： Hongju Li Wei-Cai Yang State Key Laboratory of molecular Developmental biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences

Different from animals, sessile plants are equipped with a large receptor-like kinase(RLK) superfamily. RLKs are a family of single trans-membrane proteins with divergent N-terminal extracellular domains capped by a signal peptide and C-terminal intracellular kinase. Researches in the last two decades have uncovered an increasing number of RLKs that regulate plant development, stress response and sexual reproduction, highlighting a dominant role of RLK signaling in cell-to-cell communications. Sexual reproduction in flowering plants is featured by interactions between the male gametophyte and the female tissues to facilitate sperm delivery and fertilization. Emerging evidences suggest that RLKs regulate almost every aspect of plant reproductive process, especially during pollination. Therefore, in this review we will focus mainly on the function and signaling of RLKs in plant male-female interaction and discuss the future prospects on these topics.

关键词： RLK signaling plant reproduction pollen tube female gametophyte male-female interaction pollen tube growth and guidance pollen tube reception