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Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2969-2981页

作者： Mackenzie M.spicer Jianqi Yang Daniel Fu Alison N.DeVore Marisol Lauffer Nilufer s.Atasoy Deniz Atasoy Rory A.Fisher Department of Neuroscience and Pharmacology University of Iowa Carver College of MedicineIowa CityIAUSA Iowa Neuroscience Institute University of Iowa Carver College of MedicineIowa CityIAUSA Interdisciplinary Graduate Program in Molecular Medicine University of Iowa Carver College of MedicineIowa CityIAUSA Neural Circuits and Behavior Core University of Iowa Carver College of MedicineIowa CityIAUSA

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s *** hippocampal neurogenesis is reduced in patients with Alzheimer’s *** stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s ***,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly ***,regulator of G protein signaling 6(RGs6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in ***,we generated novel RGs6fl/fl;APP_(sWE) mice and used retroviral approaches to examine the impact of RGs6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse *** found that voluntary running in APP_(sWE) mice restored their hippocampal cognitive impairments to that of control *** cognitive rescue was abolished by RGs6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal *** hippocampal neurogenesis was reduced in sedentary APP_(sWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGs6 deletion in dentate gyrus neural precursor ***6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGs6-expressing ***,RGs6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(sWE) mice,identifying RGs6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

关键词： adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus exercise learning/memory neural precursor cells regulator of G protein signaling 6(RGs6)

Impact of Zika virus non-structural protein mutations on hippocampal damage

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Neural Regeneration Research 2025年第8期20卷 2307-2308页

作者： Larissa M.G.Cassiano Roney s.Coimbra Neurogenômica/Imunopatologia Instituto RenéRachouFiocruzBelo HorizonteBrazil Departamento de Bioquímica e Imunologia Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil

The Zika virus(ZIkV),a member of the Flaviviridae family,attracted worldwide attention for its connection to severe neurological effects,notably microcephaly in newborns,first reported during the 2015 epidemic in ***,its impact goes beyond fetal and neonatal abnormalities,also affecting the central nervous system(CNs)in both children and adults,leading to enduring cognitive and behavioral impairments.

关键词： damage fetal neonatal

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

Hepatitis B among Asian Americans:Prevalence, progress, and prospects for control

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World Journal of Gastroenterology 2015年第42期21卷 11924-11930页

作者： moon s Chen Jr Julie Dang Division of Hematology and Oncology Department of Internal Medicine University of California Davis School of Medicine Sacramento University of California Davis Comprehensive Cancer Center Sacramento National Cancer Institute-funded National Center for Reducing Asian American Cancer Health Disparities University of California Davis Comprehensive Cancer Center Sacramento

After tobacco use, chronic hepatitis B(CHB) viral infections are the most important cause of cancer globally in that 1 out of 3 individuals have been infected with the hepatitis B virus(HBV). Though infection rates are low(states, Asian Americans who comprise about 6% of the population experience about 60% of the CHB burden. This paper reviews the magnitude of hepatitis B(HBV) burden among Asian Americans and the progress being made to mitigate this burden, primarily through localized, communitybased efforts to increase screening and vaccination among Asian American children, adolescents, and adults. This review brings to light that despite the numerous community-based screening efforts, a vast majority of Asian Americans have not been screened and that vaccination efforts, particularly for adults, are sub-optimal. Greater efforts to integrate screenings by providers within existing healthcare systems are urged. Evidence-based strategies are offered to implement CDC's three major recommendations to control and prevent hepatitis B through targeted screening and enhanced vaccination efforts.

关键词： Hepatitis B Asian Americans Chronic hepatitis B Va

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref kevin k.Wang J.Adrian Tyndall Binu Tharakan Firas kobeissy Department of surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse school of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Multi-omics analysis reveals the neuroprotective effect of Atractylodis Rhizoma Alba extract against Parkinson's disease in mouse

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Journal of Traditional Chinese Medicine 2024年第6期44卷 1111-1117页

作者： kANG sohi LEE soong-In moon Byeong Cheol sONG Jun Ho kIM sung-Ho moon Changjong LEE sueun kIM Chul kIM Joong sun Department of Anatomy and Convergence Medical science College of MedicineInstitute of Health SciencesGyeongsang National UniversityJinju 52727Republic of Korea College of Veterinary Medicine and Bk21 FOUR Program Chonnam National UniversityGwangju 61186Republic of Kore Department of Oriental Medicine Prescription College of Oriental MedicineDong-Shin UniversityGwangju 61186Republic of Kore Herbal Medicine Resources Research Center Korea Institute of Oriental Medicine111GeonjaeroNaju-siJeollanam-do 58245Republic of Korea Department of Biology Chungbuk National UniversityCheongju 28644Republic of Korea kM Data Division Korea Institute of Oriental Medicine1672 Yuseong-daeroYuseong-guDaejeon 34054Republic of Korea

OBJECTIVE: To assess Atractylodis Rhizoma Alba extract(ARE) neuroprotective function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated mice and related genes. METHODs: Examined m RNA-DNA methylation changes induced by ARE in MPTP-induced Parkinson's disease(PD) model's substantia nigra. REsULTs: ARE mitigated MPTP-induced motor impairment in rotarod and open field tests and preserved tyrosine hydroxylase-positive neuronal cells in substantia nigra and striatum. Genome RNA-sequencing and Methyl-sequencing in substantia nigra of vehicle/ARE-treated MPTP-induced PD mice showed 84 differentially expressed genes(DEGs) and 1804 differentially methylated regions(DMRs). Upregulated genes involved zinc ion homeostasis, cilium protein localization, and transcription;downregulated genes linked to ephrin receptor signaling, somitogenesis, and gene expression regulation. Hyper/hypomethylated DMRs post-ARE treatment associated with Wnt signaling, mitochondrial organization, dopamine biosynthesis, and hindbrain development. No significant correlation between DEGs and methylated genes related to PD pathogenesis. CONCLUsION: This research has identified the epigenetic targets of ARE's therapeutic action and gives insight on how ARE protects neurons in Parkinson's disease.

关键词： Parkinson disease nerve degeneration 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine Atractylodis Rhizoma Alba Methyl-seq

Weapon effectiveness and the shapes of damage functions

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Defence Technology（防务技术） 2021年第2期17卷 617-632页

作者： sei-Hoon moon th R&D Institute Agency for Defense DevelopmentYusungDaejeon305-152Republic of Korea Department of Mechanical and Aerospace Engineering Naval Postgraduate school MontereyCA93940USA

This paper provides a review of methods of assessing a fragmentation weapon’s effectiveness against a point target or an area target with keeping the focus on the necessity of using the Carleton damage function with the correct shape ***,cookie-cutter damage functions are redefined to preserve the shape factor of and to have the same lethal area as the corresponding Carleton damage ***,closed-form solutions of the effectiveness methods are obtained by using those cookie-cutter damage functions and the Carleton damage ***,the closed-form solutions are applied to calculate the probability of damaging a point target and the expected fractional damage to an area target for several attack scenarios by using cookie-cutter damage functions and the Carleton damage functions with different shape *** comparison of the calculation results shows that using cookie-cutter damage functions or the Carleton damage function with a wrong shape factor results in quite significant differences from using the original Carleton damage function with a correct shape factor when weapon’s delivery error deviations are less than or comparable to the lengths of the lethal area and the aim point is far from a *** effectiveness methods improved in this paper will be useful for mission planning utilizing the precision-guided munitions in circumstances where the collateral damage should be reduced.

关键词： Weapon effectiveness Point target Area target Cookie-cutter damage function Carleton damage function

Biomarkers for Parkinson's Disease:Recent Advancement

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Neuroscience Bulletin 2017年第5期33卷 585-597页

作者： sharvari Lotankar kedar s Prabhavalkar Lokesh k Bhatt Department of Pharmacology SVKM's Dr Bhanuben Nanavati College of PharmacyVile Parle(W)MumbaiIndia

As a multi-factorial degenerative disease, Parkinson＇s disease （PD） leads to tremor, gait rigidity, and hypokinesia, thus hampering normal living. As this disease is usually detected in the later stages when neurons have degenerated completely, cure is on hold, ultimately leading to death due to the lack of early diagnostic techniques. Thus, biomarkers are required to detect the disease in the early stages when prevention is possible. Various biomarkers providing early diagnosis of the disease include those of imaging, cerebrospinal fluid, oxidative stress, neuroprotection, and inflammation. Also, biomarkers, alone or in combination, are used in the diagnosis and evolution of PD. This review encompasses various biomarkers available for PD and discusses recent advances in their development.

关键词： Parkinson's disease· Imaging biomarkers ·Biochemical biomarkers - Clinical biomarkers Geneticbiomarkers

Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

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Neural Regeneration Research 2025年第1期20卷 191-192页

作者： Narek Manukjan Daniel Fulton Zubair Ahmed WMatthijs Blankesteijn sébastien Foulquier Department of Pharmacology and Toxicology Maastricht UniversityMaastrichtThe Netherlands CARIM-school for Cardiovascular Diseases Maastricht UniversityMaastrichtThe Netherlands Neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK Centre for Trauma sciences Research University of BirminghamEdgbastonBirminghamUK MHeNs-school for Mental Health and Neuroscience Maastricht UniversityMaastrichtThe Netherlands Department of Neurology Maastricht University Medical CenterMaastrichtThe Netherlands

As the population ages,the burden of age-related diseases becomes ***,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common ***,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(csVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of *** term csVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CsVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).

关键词： pathology becoming white