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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

Energy storage in Covalent Organic Frameworks: From Design Principles to Device Integration

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Chemical Research in Chinese Universities 2022年第2期38卷 356-363页

作者： DING Huimin mal Arindam WANG Cheng sauvage Center for Molecular sciences College of Chemistry and Molecular SciencesWuhan UniversityWuhan 430072P.R.China

Covalent organic frameworks(COFs) have received profound attention in recent years owing to their tailor-made porosity, large surface area and robust stability. More specifically, 2D COFs with redox-active and π electron-rich units allow efficient charge carriers hopping and ion migration, thus offering great potentials in energy storage. Herein, we present a systematic and concise overview of the recent advances in 2D COFs related to the electrochemical energy field, including supercapacitors, fuel cells, rechargeable lithium batteries, lithium-sulfur batteries, and other metal-ion batteries. In addition, a brief outlook is proposed on the challenges and prospects of COFs as electrode materials for energy storage.

关键词： Covalent organic framework Battery Capacitor Electrochemical energy storage Electrode

A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd Pharmacology&Therapeutics and Galway Neuroscience Center University of GalwayGalwayIreland

stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged froms transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

Applications of dynamical complexity theory in traditional Chinese medicine

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Frontiers of Medicine 2014年第3期8卷 279-284页

作者： Yan mal shuchen sun Chung-Kang Peng Division of Interdisciplinary Medicine and Biotechnology Beth Israel Deaconess Medical Centel Harvard Medical school Boston MA 02215USA sleep CenteR Eye Hospital China Academy of Chinese Medical Sciences Beijing 100040 China Department of Otolaryngology Guang 'anmen Hospital China Academy of Chinese Medical Sciences Beijing 100053 China Center for Dynamical Biomarkers and Translational Medicine National Central University Chung-Li Taiwan China

Traditional Chinese medicine （TCM） has been gradually accepted by the world. Despite its widespread use in clinical settings, a major challenge in TCM is to study it scientifically. This difficulty arises from the fact that TCM views human body as a complex dynamical system, and focuses on the balance of the human body, both internally and with its external environment. As a result, conventional tools that are based on reductionist approach arc not adequate. Methods that can quantify the dynamics of complex integrative systems may bring new insights and utilities about the clinical practice and evaluation of efficacy of TCM. The dynamical complexity theory recently proposed and its computational algorithm, Multiscale Entropy （MsE） analysis, are consistent with TCM concepts. This new system level analysis has been successfully applied to many health and disease related topics in medicine. We believe that there could be many promising applications of this dynamical complexity concept in TCM. In this article, we propose some promising applications and research areas that TCM practitioners and researchers can pursue.

关键词： traditional Chinese medicine Multiscale Entropy dynamical complexity system level applications

Deciphering the mechanobiology of microglia in traumatic brain injury with advanced microsystems

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Neural Regeneration Research 2025年第8期20卷 2304-2306页

作者： Anthony Procès sylvain Gabriele Univ.Grenoble Alpes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mechanobiology&Biomaterials Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary *** minutes ... 详细信息

关键词： traumatic injury damage

Community Responses to Mountain Tourism:A Case in Bhyundar Valley,Indian Himalaya

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Journal of Mountain science 2009年第4期6卷 394-404页

作者： Ram Babu singh suraj mal Chandra Prakash Kala Department of Geography Delhi School of EconomicsUniversity of Delhi Department of Geography Shaheed Bhagat Singh CollegeUniversity of Delhi Ecosystem and Environment Management Division Indian Institute of Forests Management

Tourism industry has become an important part of Indian economy,and tourism development has been,however,concentrated to a few areas. Accumulation of tourism activities has reached the critical stage in most of the tourism centers,which pose serious threats to the natural environment. The Bhyundar Valley of Nanda Devi Biosphere Reserve (NDBR) in Uttarakhand state of the Indian Himalaya is a burning example of such problems. Land use/cover changes,deforestation and accumulation of garbage are some of the negative impacts of unregulated tourism in the valley. Unsustainable activities of tourists and villagers in the valley make such problems very severe. To deal with the ongoing problems and ensure community involvement in tourism management and environmental conservation,the Biosphere Reserve Authority introduced ecotourism in the form of Eco Development Committees (EDCs) in the Bhyundar Valley. study reveals that many problems associated with tourism have been minimized to some extent with the help of EDCs but few are still prevailing in valley. However,the existing attempts to conserve the valley from the negative effects of tourism are inadequate and modifications are needed in the current initiatives.

关键词： Mountain tourism Land use change Community response Eco development committee Environmental management

Understanding activity of butyrate at a cellular level

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Neural Regeneration Research 2025年第8期20卷 2323-2324页

作者： Prapti Chakraborty Angela s.Laird Macquarie University Motor Neuron Disease Research Centre Macquarie Medical SchoolFaculty of MedicineHealth and Human SciencesMacquarie UniversitySydneyAustralia

Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the *** the years,butyrate has attracted ... 详细信息

关键词： carbons butyrate fiber

Microglial dysfunction and genetic risk for neurodegenerative disease

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Neural Regeneration Research 2025年第5期20卷 1401-1402页

作者： Debra s.MacDonald Jay Penney Department of Biomedical sciences AVCUniversity of Prince Edward IslandCharlottetownPECanada

Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases a re increasing in prevalence as world populations *** tremendous progress has been made,our understanding of the mechanisms that underlie the development of these diseases remains far from com *** troubling,despite the growing emotional and financial toll being to ken by neurodegenerative disorders,existing treatment options are limited almost exclusively to those that help manage symptoms but that lack the ability to alter the progression of the disease(Liu et al.,2022).

关键词： degenerative diseases