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

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 c.toskeletons. 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 c.tokine. 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

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor cilleros-Mañé Laia Just-Borràs Marta Balanyà-Segura Aleksandra Polishchuk laura Nadal Marta Tomàs carolina Silvera-Simón Manel M.Santafé Maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and c(PKA and PKc)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKc activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

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Neural Regeneration Research 2025年第10期20卷 2872-2886页

作者： Marta chierichetti Riccardo cristofani Valeria crippa Veronica Ferrari Marta cozzi Elena casarotto Paola Pramaggiore laura cornaggia Guglielmo Patelli Ali Mohamed Margherita Piccolella Mariarita Galbiati Paola Rusmini Barbara Tedesco Angelo Poletti Laboratory of Experimental Biology Dipartimento di Scienze Farmacologiche e Biomolecolari“Rodolfo Paoletti”(DiSFeB)Universitàdegli Studi di MilanoMilanItaly

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock ***8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and ***8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective *** line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and *** cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under ***,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar *** note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other *** is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial *** review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its ***-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

关键词： aggregation autophagy cancer chaperone chaperone-assisted selective autophagy cognitive impairment HSPB8 neuroinflammation neuromuscular diseases therapy

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Infertility treatment, a matter of a lovely sperm？

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Asian Journal of Andrology 2013年第6期15卷 719-720页

作者： laura c Giojalas centro de Biologfa celular y Molecular & Instituto deInvestigaciones Biol6gicas y Tecnol6gicas (cONIcET-Universidad Nacional de cordoba) Av. Velez Sasrfield1611 X5016GCA - Cordoba Argentina

Nowadays, the efficiency of the infertil-ity treatment is relatively low. One of the cues to counteract this problem relies on the optimum selection of spermatozoa. We developed a new method （sperm selection assay （SSA）） based on the chemical attrac-tion of spermatozoa that are at the best functional state. Additionally, the SSA leads spermatozoa to complete and/or acquire the competence to fertilize the egg. These effects are equally observed either in nor-mal or subfertile semen samples. Those cap-abilities of SSA may improve the success of current infertility treatment.

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Skeletal muscle mitochondrial health and spinal cord injury

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World Journal of Orthopedics 2016年第10期7卷 628-637页

作者： laura c O'Brien Ashraf S Gorgey Spinal cord Injury and Disorders Service Hunter Holmes McGuire VA Medical Center Department of Physiology and Biophysics Virginia Commonwealth University Department of Physical Medicine and Rehabilitation Virginia Commonwealth University

Mitochondria are the main source of cellular energy production and are dynamic organelles that undergo biogenesis, remodeling, and degradation. Mitochondrial dysfunction is observed in a number of disease states including acute and chronic central or peripheral nervous system injury by traumatic brain injury, spinal cord injury(ScI), and neurodegenerative disease as well as in metabolic disturbances such as insulin resistance, type Ⅱ diabetes and obesity. Mitochondrial dysfunction is most commonly observed in high energy requiring tissues like the brain and skeletal muscle. In persons with chronic ScI, changes to skeletal muscle may include remarkable atrophy and conversion of muscle fiber type from oxidative to fast glycolytic, combined with increased infiltration of intramuscular adipose tissue. These changes contribute to a proinflammatory environment, glucose intolerance and insulin resistance. The loss of metabolically active muscle combined with inactivity predisposes individuals with ScI to type Ⅱ diabetes and obesity. The contribution of skeletal muscle mitochondrial density and electron transport chain activity to the development of the aforementioned comorbidities following ScI is unclear. A better understanding of the mechanisms involved in skeletal muscle mitochondrial dynamics is imperative to designing and testing effective treatments for this growing population. The current editorial will review ways to study mitochondrial function and the importance of improving skeletal muscle mitochondrial health in clinical populations with a special focus on chronic ScI.

关键词： Mitochondria Spinal cord injuries Body composition Diabetes mellitus Obesity Metabolism

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Design and guidance of a multi-active debris removal mission

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Astrodynamics 2023年第4期7卷 383-399页

作者： Minduli c.Wijayatunga(B) Roberto Armellin Harry Holt laura Pirovano Aleksander A.Lidtke Te Pūnaha Atea–Space Institute The University of AucklandAuckland 1010New Zealand Astroscale Japan Inc. 1-16-4-16 KinshiSumida-kuTokyoJapan

Space debris have become exceedingly dangerous over the years as the number of objects in orbit continues to *** debris removal(ADR)missions have gained significant interest as effective means of mitigating the risk of collision between objects in *** study focuses on developing a multi-ADR mission that utilizes controlled reentry and *** mission comprises two spacecraft:a Servicer that brings debris to a low altitude and a Shepherd that rendezvous with the debris to later perform a controlled reentry.A preliminary mission design tool(PMDT)was developed to obtain time and fuel optimal trajectories for the proposed mission while considering the effect of J2,drag,eclipses,and duty *** PMDT can perform such trajectory optimizations for multi-debris missions with computational time under a *** guidance schemes are also studied,taking the PMDT solution as a reference to validate the design methodology and provide guidance solutions to this complex mission profile.

关键词： active debris removal(ADR) trajectory design optimization autonomous guidance low-thrust electric propulsion △u-law guidance Q-law guidance

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Determination of gluten immunogenic peptides for the management of the treatment adherence of celiac disease: A systematic review

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World Journal of Gastroenterology 2021年第37期27卷 6306-6321页

作者： laura c.to Irati Mendia carolina Sousa Julio césar Bai Angel cebolla Research and Development BiomedalCamas 41900SevilleSpain Human Nutrition and Food Science Doctoral Program University of GranadaGranada 18011Spain Molecular Biology Biomedicine and Clinical Research Doctoral ProgramUniversity of SevilleSeville 41012Spain Department of Microbiology and Parasitology University of SevilleSeville 41013Spain Department of Gastroenterology Dr.Carlos Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1264Argentina Research Institutes Universidad del SalvadorBuenos Aires 1050Argentina

BAcKGROUND Gluten is a complex mixture of proteins with immunogenic peptide sequences triggering the autoimmune activity in patients with celiac disease(ceD).Gluten immunogenic peptides(GIP)are resistant to gastrointestinal digestion and are then excreted via the stool and *** common detection methods applied in the follow-up visits for ceD patients such as serology tests,dietetic interviews,questionnaires,and duodenal biopsy have been proved to be inefficient,invasive,or inaccurate for evaluating gluten-free diet(GFD)*** of excreted GIP in stool and urine has been developed as a non-invasive,direct,and specific test for GFD *** To summarize published literature about the clinical utility of GIP determination in comparison to the tools employed for GFD *** PubMed and Web of Science searches were performed using the keywords“gluten immunogenic peptides”or“gluten immunogenic peptide”and a combination of the previous terms with“feces”,“stools”,“urine”,“celiac disease”,“gluten-free diet”,and“adherence”to identify relevant clinical studies published in English and Spanish between 2012 to January *** lists from the articles were reviewed to identify additional pertinent *** articles and abstracts reporting the clinical use of GIP determination in stool and/or urine for the follow-up of patients with ceD in comparison with other tools in use were *** reports,commentaries,reviews,conference papers,letters,and publications that did not focus on the aims of this review were *** Total of 15 publications were found that involved the use of GIP determination in stool and/or urine to monitor the adherence to the GFD in comparison to other *** included both children and adults diagnosed with ceD and healthy ***,these preliminary studies indicated that this novel technique was highly sensitive for the detection of GFD transgressions and therefore could fac

关键词： celiac disease Gluten-free diet Gluten immunogenic peptides Immunoassays Stool Urine

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Microbiome and colorectal carcinogenesis:Linked mechanisms and racial differences

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World Journal of Gastrointestinal Oncology 2022年第2期14卷 375-395页

作者： Sofia c.tortora Vimal M Bodiwala Andrew Quinn laura A Martello Shivakumar Vignesh Department of Medicine and Division of Gastroenterology&Hepatology SUNY Downstate Health Sciences UniversityBrooklynNY 11203United States

Various studies have shown the interplay between the intestinal microbiome,environmental factors,and genetic changes in colorectal cancer(cRc)*** this review,we highlight the various gut and oral microbiota associated with cRc and colorectal adenomas,and their proposed molecular mechanisms in relation to the processes of“the hallmarks of cancer”,and differences in microbial diversity and abundance between race/*** with cRc showed increased levels of Bacteroides,Prevotella,Escherichia coli,enterotoxigenic Bacteroides fragilis,Streptococcus gallolyticus,Enterococcus faecalis,Fusobacterium nucleatum(***)and clostridium *** levels of Bacteroides have been found in African American(AA)compared to caucasian American(cA)***-inflammatory bacteria such as *** and Enterobacter species were significantly higher in ***,AA patients have been shown to have decreased microbial diversity compared to cA *** studies have shown that using microbiome profiles in conjunction with certain risk factors such as age,race and body mass index may help predict healthy colon vs one with adenomas or *** is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic *** condition causes increased systemic inflammation,immune dysregulation,gut microbiota dysbiosis and thereby possibly influencing colorectal ***-associated bacteria such as Fusobacterium,Prevotella,Bacteroides and Porphyromonas have been found in cRc tissues and in feces of cRc ***,a deeper understanding of the association between oral and gastrointestinal bacterial profile,in addition to identifying prevalent bacteria in patients with cRc and the differences observed in ethnicity/race,may play a pivotal role in predicting incidence,prognosis,and lead to the development of new treatments.

关键词： colorectal cancer Oral microbiome Gut microbiome Hallmarks of cancer Racial/ethnic microbial diversity

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Designated critical habitats for *** species are not protected from climate and land-use change

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Geography and Sustainability 2024年第3期5卷 482-490页

作者： Aimee Delach laura A.Nunes Alex Borowicz Theodore c.Weber center for conservation Innovation Defenders of Wildlife113017th Street NWWashingtonD.C.20036United States

Designation of critical habitat is an important conservation tool for species listed as threatened or endangered under the United States(U.S.)Endangered Species Act(ESA).While this is an important protective mechanism,lands designated as critical habitat could still be subject to degradation and fragmentation if they are not also in a protected status that prioritizes biodiversity ***,most designations of critical habitat do not explicitly take climate change into *** objective of our study was to determine whether and to what extent critical habitats for species listed under the ESA are located within protected areas and areas previously identified as climate refugia or climate corridors,to inform management strategies to better conserve and recover these *** mapped the designated critical habitats of 153 ESA-listed species and measured their overlap with previously-identified areas of climate refugia and corridors(cRc),and also with lands designated as nature-protected by *** Survey’s Gap Analysis Project(GAP Status 1 or 2)and working lands with wildlife habitat potential(GAP Status 3).Only 18%of all designated critical habitat is located on lands that are both in cRc and nature-protected,and only 9%of species had over half of their designated critical habitats in such lands.84%of species hadcritical habitats with these *** habitats may therefore not fulfill their essential role of helping imperiled species persist and recover.

关键词： Endangered Species Act critical habitat climate refugia climate corridors Protected areas Biodiversity conservation

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conservation of natural enemy fauna in citrus canopies by horticultural mineral oil： comparison with effects of carbaryl and methidathion treatments for control of armored scales

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Insect Science 2010年第5期17卷 414-426页

作者： Weiguang Liang Alan Meats G. Andrew c. Beattie Robert Spooner-Hartt laura Jiang centre for Plant and Food Sciences University of Western Sydney School of Biological Sciences University of Sydney Sydney New South Wales Austrafia

The disruptive effects of an nc24 horticultural mineral oil （HMO） and two other insecticides （carbaryl and methidathion） on two armored scale insects and natural enemy fauna were evaluated in two citrus orchards. In the first orchard, all three spray treatments and non-sprayed controls were distributed separately among individual trees in one block, whereas in the second orchard the control, HMO and methidathion treatments were applied at the level of whole blocks. The results in both orchards were similar. All three of the spray treatments had a lethal effect on the red scale insects and the effects of HMO and methidathion tested at the second site lasted for at least 19 weeks and for purple scale, at least 50 weeks. HMO did not have a significant effect on the abundance and species diversity of parasitoids and （for the most part） did not affect coccinellids and predatory mites. Both carbaryl and methidathion caused significant ongoing disruption to the above groups. No treatment resulted in the resurgence of the scale insects or the outbreak ofphytophagous mites, even where whole blocks were sprayed.

关键词： conservation HMO replacement resurgence water saving

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