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Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 241-254页

作者： Chenjun Hu Yiqun Yan Yanhong Jin Jun Yang Yongmei Xi Zhen Zhong department of Neurology of the Second Afliated Hospital and department of human Anatomy Histology and EmbryologyZhejiang University School of MedicineHangzhou 310058China department of Physiology and department of Cardiology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Division of human Reproduction and Developmental genetics Women’s Hospital and Institute of GeneticsZhejiang University School of MedicineHangzhou 310006China

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral *** a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into *** and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent *** review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and *** on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also *** lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关键词： Neurodegenerative diseases Prion-like propagation Seeding Endocytosis Endolyosomal leaking Degradation

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

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Neural Regeneration Research 2024年第7期19卷 1584-1592页

作者： Jong Mi Park Masoud Rahmati Sang Chul Lee Jae Il Shin Yong Wook Kim department and Research Institute of Rehabilitation Medicine Yonsei University College of MedicineSeoulSouth Korea department of Physical Education and Sport Sciences Faculty of Literature and Human SciencesLorestan UniversityKhoramabadIran department of pediatrics Yonsei University College of MedicineSeoulSouth Korea

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease *** cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s *** stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of *** performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal *** searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,*** study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control *** use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the *** with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational *** the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a

关键词： animal animal experimentation mesenchymal stem cells models Parkinson’s disease stem cell transplantation

Neuron-to-astrocyte proteostatic stress signaling in response to tau pathology

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Neural Regeneration Research 2024年第3期19卷 505-506页

作者： Kevin Llewelyn Batenburg Wiep Scheper Amsterdam UMC location Vrije Universiteit Amsterdam Department of Human GeneticsAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands department of Functional Genomics Center for Neurogenomics and Cognitive ResearchVrije Universiteit AmsterdamAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands

Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of *** is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their *** proteostatic stress responses are in place to protect cells from damage in case of proteostatic *** integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.

关键词： translation stress Together

Changes in children’s cardiorespiratory fitness and body mass index over the course of the COVID‑19 pandemic:a 34‑month longitudinal study of 331 primary school children

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World Journal of pediatrics 2024年第2期20卷 185-188页

作者： Gerald Jarnig Reinhold Kerbl Mireille N.M.van Poppel Institute of human Movement Science Sport and HealthUniversity of GrazMozartgasse 148010 GrazAustria department of pediatrics and Adolescent Medicine LKH Hochsteiermark8700 LeobenAustria

In late 2019,heavy restrictions were enforced on public activities worldwide to diminish the spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus[1].These restrictions,which included school closures and strictly limited sports and leisure opportunities,particularly impacted children and adolescents[2].Lifestyle changes in children and adolescents led to reduced physical activity levels[2,3],increased sedentary behavior[3,4],changes in eating habits,and changes in sleep habits[3].

关键词： respiratory acute children

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

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World Journal of Diabetes 2024年第4期15卷 606-622页

作者： Ashwin Kumar Shukla Komal Awasthi Kauser Usman Monisha Banerjee Molecular and human genetics Laboratory Department of ZoologyUniversity of LucknowLucknow 226007Uttar PradeshIndia department of Medicine King Georges’Medical UniversityLucknow 226003Uttar PradeshIndia Institute of Advanced Molecular genetics and Infectious Diseases(IAMGID)University of LucknowLucknow 226007Uttar PradeshIndia

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 *** has affected over 768 million people worldwide,resulting in approx-imately 6900000 ***-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney *** indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic *** the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 *** converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a *** ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and *** ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 *** review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in *** treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

关键词： Angiotensin-converting enzyme 2 Angiotensin-converting enzyme inhibitors Angiotensin-II receptor blockers Complex diseases COVID-19 Type 2 diabetes

Therapeutic potential and pharmacological mechanism of visnagin

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Journal of Integrative Medicine 2024年第4期22卷 399-412页

作者： Poonam Yadav Sumeet Kumar Singh Sayantap Datta Saloni Verma Aarti Verma Arnab Rakshit Anjana Bali Jasvinder Singh Bhatti Amit Khurana Umashanker Navik department of Pharmacology School of Health SciencesCentral University of PunjabBathindaPunjab 151401India department of Pharmacological and Pharmaceutical Sciences College of PharmacyUniversity of HoustonHoustonTX 77204-5000USA department of human genetics and Molecular Medicine School of Health SciencesCentral University of PunjabBathindaPunjab 151401India

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga(L.)Lam(a synonym of Visnaga daucoides Gaertn.)plant,which is used to cure various *** investigations into the bioactive properties of visnagin have been studied to *** literature on visnagin demonstrates its biological properties,including anti-inflammatory,anti-diabetic,and beneficial effects in cardiovascular and renal ***,visnagin improves sperm quality parameters,stimulates steroidogenesis,and increases serum gonadotropins and testosterone levels,while decreasing proinflammatory cytokines,oxidative damage,genomic instability,and it modulates ***,visnagin has emerged as an exciting lead for further research,owing to its potential in various unmet clinical *** current review summarized its basic structure,pharmacokinetics,and pharmacological effects,focusing on its mechanisms of *** review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin’s safe clinical use.

关键词： Visnagin Phytochemical Anti-inflammatory Ammi visnaga L. Visnaga daucoides Gaertn Cancer

Exome sequencing identifies a likely causative variant in 53%of families with ciliopathy-related features on renal ultrasound after excluding NPHP1 deletions

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Genes & Diseases 2024年第5期11卷 40-43页

作者： Konstantin Deutsch Verena Klambt Thomas M.Kitzler Tilman Jobst-Schwan Ronen Schneider Florian Buerger Steve Seltzsam Sherif El Desoky Jameela A.Kari Farkhanda Hafeez Maria Szczepanska Loai A.Eid Hazem S.Awad Muna Al-Saffar Neveen A.Soliman Velibor Tasic Camille Nicolas-Frank Kirollos Yousef Luca M.Schierbaum Sophia Schneider Abdul Halawi Izzeldin Elmubarak Katharina Lemberg Shirlee Shril Shrikant M.Mane Nancy Rodig Friedhelm Hildebrandt Division of Nephrology Department of PediatricsBoston Children’s HospitalHarvard Medical SchoolBostonMA 02215USA department of Pediatric Gastroenterology Nephrology and Metabolic DiseasesCharite Universitatsmedizin BerlinBerlin 13353Germany Berlin Institute of Health at Charitee Universitatsmedizin Berlin BIH Biomedical Innovation AcademyBIH Charite Clinician Scientist ProgramBerlin 10178Germany department of Nephrology and Hypertension FriedrichAlexander-Universitat Erlangen-NurnbergErlangen 91054Germany department of pediatrics Faculty of Medicine King Abdulaziz UniversityPediatric Nephrology Center of ExcellenceKing Abdulaziz University HospitalJeddah 21589Saudi Arabia department of Pediatric Nephrology The Children’s Hospital and Institute of Child HealthLahore 54000Pakistan department of pediatrics Faculty of Medical Sciences in ZabrzeMedical University of Silesia in KatowiceKatowice 40-752Poland Dubai Hospital and Al-Jalila Children’s Specialty Hospital Kidney Center of ExcellenceDubai 4545United Arab Emirates department of genetics and Genomics UAE UniversityAbu Dhabi 15551United Arab Emirates department of pediatrics Division of Genetics and GenomicsBoston Children’s HospitalHarvard Medical SchoolBostonMA 02215USA department of pediatrics Center of Pediatric Nephrology and TransplantationKasr Al Ainy School of MedicineCairo UniversityCairo 11562Egypt Egypt Center for Research and Regenerative Medicine(ECRRM) Cairo 11511Egypt Medical Faculty Skopje University Children’s HospitalSkopje 1000North Macedonia department of genetics Yale University School of MedicineNew HavenCT 06520USA

Nephronophthisis-related ciliopathies(NPHP-RC)represent one of the most common causes of chronic kidney disease in the first three decades of life and are characterized by a broad genetic and clinical heterogeneity.1 To date,more than 90 genes have been identified that cause autosomalrecessive NPHP-RC if mutated,accounting for up to 60%of cases.1 Among these,homozygous deletions of NPHP1 are the most common *** genes localize to primary cilia,basal bodies,or the centrosome and lead to a primary ciliary disruption if mutated,thereby causing a broad phenotypical spectrum.1 Patients that suffer from NPHP-RC can either have an isolated renal phenotype,such as polyuria,polydipsia,decreased urinary concentration ability,and secondary enuresis due to loss of tubular function,or present with extrarenal symptoms including retinal degeneration,cerebellar vermis hypoplasia,or hepatic *** are often diagnosed in early adolescence,reaching end-stage renal disease before 25 years of age,but early onset and rapidly progressive forms of NPHP-RC also exist.1 Renal ultrasound indicates kidneys of normal or reduced renal length with increased echogenicity and corticomedullary cysts.

关键词： degeneration urinary likely

Structure of a histone hexamer bound by the chaperone domains of SPT16 and MCM2

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Science China(Life Sciences) 2024年第6期67卷 1305-1307页

作者： Songlin Gan Wen-Si Yang Liting Wei Zhiguo Zhang Rui-Ming Xu Key Laboratory of Epigenetic Regulation and Intervention Institute of BiophysicsChinese Academy of SciencesBeijing 100101China School of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Institute for Cancer genetics Department of Pediatrics and Department of Genetics and DevelopmentColumbia University Irving Medical CenterNew York 10032USA School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China

Dear Editor,The passage of DNA replication forks during eukaryotic cell division disrupts the nucleosomes they encounter,and de novo assembly of nucleosomes onto replicated DNA must take place to restore chromatin ***... 详细信息

关键词： structure nucleosome passage

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Clinical-DNA Correlates of Anxiety in Patients with Ehlers-Danlos Syndrome

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Open Journal of Psychiatry 2024年第4期14卷 319-333页

作者： Golder N. Wilson Vijay S. Tonk department of pediatrics Texas Tech University Health Sciences Center Lubbock TX USA Kinder Genome genetics Private Practice Dallas TX USA Medical genetics and the Cytogenomic Laboratory Department of Pediatrics Texas Tech University Health Sciences Center Lubbock TX USA

Introduction: Anxiety disorders have a lifetime prevalence of 34% with a similar level of heritability (31%) yet lack objective markers that could differentiate patients with underlying conditions. Up to 60%-70% of patients with Ehlers-Danlos syndrome have anxiety that meets criteria of generalized anxiety disorder, their clinical-DNA findings worth examining as biomarkers for patients with generalized anxiety. Method: Of the 1899 patients diagnosed with Ehlers-Danlos syndrome, 1261 were systematically evaluated for 80 history and 40 physical findings and separated into 826 who reported anxiety and 435 who did not. The most consistently reported or management-directing 60 of these clinical findings were, along with variations in genes relevant to these disorders, examined for association with anxiety. Results: Among the 30 anxiety- associated findings judged most predictive of Ehlers-Danlos syndrome in patients with anxiety were expected ones of adrenergic stimulation (difficulty concentrating-87% frequency and 1.26 anxiety/no anxiety ratio;chronic fatigue-84%, 1.17;sleep issues 69%, 1.52 that are criteria for generalized anxiety disorder) or of cholinergic suppression (e.g., frequent nausea 64%, 1.26). Less associated but more discriminating for underlying disease were those reflective of neuromuscular impact (e.g., chronic daily headaches 76%, 1.12);hypermobility (e.g., awareness of flexibility 72%, 1.03), or skin changes (e.g., elasticity around jaw 71%, 1.06). Anxiety-associated DNA variants included 54 of 88 in collagen type I/V/VII/IX genes, 14 of 16 in sodium channel SCN9A/10A/ 11A genes, 59 of 85 in POLG/MT-DNA genes, and 21 of 28 in profilaggrin- FLG genes that respectively impacted tissue laxity, sensory neural, autonomic-mitochondrial, and autonomic-inflammatory functions. Conclusion: Analysis of pathogenetic mechanisms in Ehlers-Danlos syndrome selected some 50 clinical-DNA findings useful for its diagnosis in those with generalized anxiety disorders.

关键词： Anxiety Generalized Anxiety Disorder Ehlers-Danlos Syndrome Long COVID19 Joint Hypermobility Dysautonomia DNA Testing Whole Exome Sequencing DNA Variant Qualification