Neuropathology and Applied Neurobiology最新文献_第5页

Targeting the EGFR pathway: An alternative strategy for the treatment of tuberous sclerosis complex? 靶向表皮生长因子受体通路：治疗结节性硬化症复合体的另一种策略？

IF 5 2区医学

Neuropathology and Applied Neurobiology Pub Date : 2024-04-01 DOI: 10.1111/nan.12974

Julia Schachenhofer, Victoria-Elisabeth Gruber, Stefanie Valerie Fehrer, Carmen Haider, Sarah Glatter, Ewa Liszewska, Romana Höftberger, Eleonora Aronica, Karl Rössler, Jacek Jaworski, Theresa Scholl, Martha Feucht

{"title":"Targeting the EGFR pathway: An alternative strategy for the treatment of tuberous sclerosis complex?","authors":"Julia Schachenhofer, Victoria-Elisabeth Gruber, Stefanie Valerie Fehrer, Carmen Haider, Sarah Glatter, Ewa Liszewska, Romana Höftberger, Eleonora Aronica, Karl Rössler, Jacek Jaworski, Theresa Scholl, Martha Feucht","doi":"10.1111/nan.12974","DOIUrl":"10.1111/nan.12974","url":null,"abstract":"Introduction: Tuberous sclerosis complex (TSC) is caused by variants in TSC1/TSC2, leading to constitutive activation of the mammalian target of rapamycin (mTOR) complex 1. Therapy with everolimus has been approved for TSC, but variations in success are frequent. Recently, caudal late interneuron progenitor (CLIP) cells were identified as a common origin of the TSC brain pathologies such as subependymal giant cell astrocytomas (SEGA) and cortical tubers (CT). Further, targeting the epidermal growth factor receptor (EGFR) with afatinib, which is expressed in CLIP cells, reduces cell growth in cerebral TSC organoids. However, investigation of clinical patient-derived data is lacking.Aims: Observation of EGFR expression in SEGA, CT and focal cortical dysplasia (FCD) 2B human brain specimen and investigation of whether its inhibition could be a potential therapeutic intervention for these patients.Methods: Brain specimens of 23 SEGAs, 6 CTs, 20 FCD2Bs and 17 controls were analysed via immunohistochemistry to characterise EGFR expression, cell proliferation (via Mib1) and mTOR signalling. In a cell-based assay using primary patient-derived cells (CT n = 1, FCD2B n = 1 and SEGA n = 4), the effects of afatinib and everolimus on cell proliferation and cell viability were observed.Results: EGFR overexpression was observed in histological sections of SEGA, CT and FCD2B patients. Both everolimus and afatinib decreased the proliferation and viability in primary SEGA, tuber and FCD2B cells.Conclusion: Our study demonstrates that EGFR suppression might be an effective alternative treatment option for SEGAs and tubers, as well as other mTOR-associated malformations of cortical development, including FCD2B.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"50 2","pages":"e12974"},"PeriodicalIF":5.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanisms of COVID-19-associated olfactory dysfunction. COVID-19 相关嗅觉功能障碍的机理。

IF 4 2区医学

Neuropathology and Applied Neurobiology Pub Date : 2024-04-01 DOI: 10.1111/nan.12960

Koping Chang, Thomas Zaikos, Nicholas Kilner-Pontone, Cheng-Ying Ho

{"title":"Mechanisms of COVID-19-associated olfactory dysfunction.","authors":"Koping Chang, Thomas Zaikos, Nicholas Kilner-Pontone, Cheng-Ying Ho","doi":"10.1111/nan.12960","DOIUrl":"10.1111/nan.12960","url":null,"abstract":"Olfactory dysfunction is one of the most common symptoms of COVID-19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has significantly decreased with the emergence of the Omicron variant, which has since become the dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID-19-associated olfactory dysfunction an ongoing health concern. The proposed pathogenic mechanisms of COVID-19-associated olfactory dysfunction are complex and likely multifactorial. While evidence suggests that infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, alterations in other components of the olfactory system (e.g., olfactory receptor neuron dysfunction, olfactory bulb injury and alterations in the olfactory cortex) may lead to persistent, long-term olfactory dysfunction. This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations and current understanding of the pathogenic mechanisms of COVID-19-associated olfactory dysfunction.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"50 2","pages":"e12960"},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10906737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Argyrophilic grain disease and co-pathologies in an older patient with a rapidly progressive neuropsychiatric syndrome. 一名患有快速进展性神经精神综合征的老年患者的霰粒肿和并发症。

IF 5 2区医学

Neuropathology and Applied Neurobiology Pub Date : 2024-04-01 DOI: 10.1111/nan.12973

Camilla N Clark, Norman Poole, Jeremy D Isaacs, Andrew D MacKinnon, Philip Rich, Leslie R Bridges, Zane Jaunmuktane, Elizabeth Caruana Galizia

引用次数: 0

Chronic traumatic encephalopathy neuropathologic change in former Australian rugby players 前澳大利亚橄榄球运动员的慢性创伤性脑病神经病理变化

IF 5 2区医学

Neuropathology and Applied Neurobiology Pub Date : 2024-03-19 DOI: 10.1111/nan.12972

Claire E. Shepherd, Heather McCann, Catriona A. McLean, Grant L. Iverson, Andrew J. Gardner

{"title":"Chronic traumatic encephalopathy neuropathologic change in former Australian rugby players","authors":"Claire E. Shepherd, Heather McCann, Catriona A. McLean, Grant L. Iverson, Andrew J. Gardner","doi":"10.1111/nan.12972","DOIUrl":"https://doi.org/10.1111/nan.12972","url":null,"abstract":"AimsWe applied the 2021 consensus criteria for both chronic traumatic encephalopathy neuropathological change and traumatic encephalopathy syndrome in a small case series of six former elite‐level Australian rugby code players.MethodsNeuropathological assessment of these cases was carried out at the Sydney and Victorian Brain Banks. Clinical data were collected via clinical interviews and health questionnaires completed by the participants and/or their next of kin, and neuropsychological testing was conducted with participants who were capable of completing this testing.ResultsAll cases exhibited progressive cognitive impairment during life. Chronic traumatic encephalopathy neuropathological change was identified in four out of the six cases. However, coexisting neuropathologies were common, with limbic‐predominant age‐related TDP‐43 encephalopathy and ageing‐related tau astrogliopathy seen in all cases, intermediate or high Alzheimer's disease neuropathological change seen in four cases and hippocampal sclerosis seen in two of the six cases.ConclusionThe presence of multiple neuropathologies in these cases complicates clinical diagnostic efforts for traumatic encephalopathy syndrome. It will be important for further clinicopathological studies on larger groups to report all neuropathological comorbidities found in cases diagnosed with either chronic traumatic encephalopathy neuropathological change and/or traumatic encephalopathy syndrome.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"1152 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140169079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Changes in the locus coeruleus during the course of Alzheimer's disease and their relationship to cortical pathology 阿尔茨海默氏症病程中神经节的变化及其与大脑皮层病理学的关系

IF 5 2区医学

Neuropathology and Applied Neurobiology Pub Date : 2024-02-05 DOI: 10.1111/nan.12965

Rebecca Beardmore, Matthew Durkin, Faizan Zayee-Mellick, Laurie C. Lau, James A. R. Nicoll, Clive Holmes, Delphine Boche

引用次数: 0

Diagnostic value of CSF chromogranin A to discriminate between Alzheimer's disease and dementia with Lewy bodies 脑脊液嗜铬粒蛋白 A 在区分阿尔茨海默病和路易体痴呆症方面的诊断价值

IF 5 2区医学

Neuropathology and Applied Neurobiology Pub Date : 2024-02-01 DOI: 10.1111/nan.12961

Olivier Bousiges, Thomas Lavaux, Catherine Demuynck, Caroline Schaeffer-Agalède, Nathalie Philippi, Candice Muller, Benjamin Cretin, Frédéric Blanc

引用次数: 0

Change in the molecular properties of CH1641 prions after transmission to wild-type mice: Evidence for a single strain. CH1641朊病毒传给野生型小鼠后分子特性的变化：单一菌株的证据

IF 5 2区医学

Neuropathology and Applied Neurobiology Pub Date : 2024-02-01 DOI: 10.1111/nan.12963

Lucien J M van Keulen, Corry H Dolstra, Ruth Bossers-de Vries, Alex Bossers, Jorg G Jacobs, Thierry Baron, Juan Maria Torres, Jan P M Langeveld

{"title":"Change in the molecular properties of CH1641 prions after transmission to wild-type mice: Evidence for a single strain.","authors":"Lucien J M van Keulen, Corry H Dolstra, Ruth Bossers-de Vries, Alex Bossers, Jorg G Jacobs, Thierry Baron, Juan Maria Torres, Jan P M Langeveld","doi":"10.1111/nan.12963","DOIUrl":"10.1111/nan.12963","url":null,"abstract":"Aim: CH1641 was discovered in 1970 as a scrapie isolate that was unlike all other classical strains of scrapie isolated so far. We performed bio-assays of CH1641 in mice in order to further characterise this specific isolate.Methods: We inoculated the original CH1641 isolate into ovine and bovine prion protein (PrP) transgenic mice as well as wild-type mice. In addition, we performed cross- and back passages between the various mouse lines to examine if one identical prion strain was isolated in all mouse lines or whether multiple prion strains exist in CH1641.Results: We report the first successful transmission of CH1641 to wild-type RIII mice and via RIII mice to wild-type VM mice. Unexpectedly, analysis of the protease-resistant prion protein (PrPres ) in wild-type mice showed a classical scrapie banding pattern differing from the banding pattern of the original CH1641 isolate. Cross- and back passages of CH1641 between the various mouse lines confirmed that the same prion strain had been isolated in all mouse lines.Conclusions: The CH1641 isolate consists of a single prion strain but its molecular banding pattern of PrPres differs between wild-type mice and PrP transgenic mice. Consequently, molecular banding patterns of PrPres should be used with caution in strain typing since they do not solely depend on the properties of the prion strain but also on the host prion protein.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"50 1","pages":"e12963"},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inflammatory bowel disease induces pathological α-synuclein aggregation in the human gut and brain. 炎症性肠病诱导人体肠道和大脑中α-突触核蛋白的病理性聚集。

IF 5 2区医学

Neuropathology and Applied Neurobiology Pub Date : 2024-02-01 DOI: 10.1111/nan.12962

Ana M Espinosa-Oliva, Rocío Ruiz, Manuel Sarmiento Soto, Antonio Boza-Serrano, Ana I Rodriguez-Perez, María A Roca-Ceballos, Juan García-Revilla, Marti Santiago, Sébastien Serres, Vasiliki Economopoulus, Ana E Carvajal, María D Vázquez-Carretero, Pablo García-Miranda, Oxana Klementieva, María J Oliva-Martín, Tomas Deierborg, Eloy Rivas, Nicola R Sibson, José L Labandeira-García, Alberto Machado, María J Peral, Antonio J Herrera, José L Venero, Rocío M de Pablos

{"title":"Inflammatory bowel disease induces pathological α-synuclein aggregation in the human gut and brain.","authors":"Ana M Espinosa-Oliva, Rocío Ruiz, Manuel Sarmiento Soto, Antonio Boza-Serrano, Ana I Rodriguez-Perez, María A Roca-Ceballos, Juan García-Revilla, Marti Santiago, Sébastien Serres, Vasiliki Economopoulus, Ana E Carvajal, María D Vázquez-Carretero, Pablo García-Miranda, Oxana Klementieva, María J Oliva-Martín, Tomas Deierborg, Eloy Rivas, Nicola R Sibson, José L Labandeira-García, Alberto Machado, María J Peral, Antonio J Herrera, José L Venero, Rocío M de Pablos","doi":"10.1111/nan.12962","DOIUrl":"10.1111/nan.12962","url":null,"abstract":"Aims: According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons.Methods: We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology.Results: Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD aetiology. Additionally, we have analysed the effect of a DSS-based rat model of gut inflammation to demonstrate (i) the appearance of P-α-syn inclusions in both Auerbach's and Meissner's plexuses (gut), (ii) an increase in α-syn expression in the ventral mesencephalon (brain) and (iii) the degeneration of nigral dopaminergic neurons, which all are considered classical hallmarks in PD.Conclusion: These results strongly support the plausibility of Braak's hypothesis and emphasise the significance of peripheral inflammation and the gut-brain axis in initiating α-syn aggregation and transport to the substantia nigra, resulting in neurodegeneration.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"50 1","pages":"e12962"},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative interactome mapping of Tau-protein in classical and rapidly progressive Alzheimer's disease identifies subtype-specific pathways. 典型阿尔茨海默病和快速进展性阿尔茨海默病中 Tau 蛋白的相互作用组比较图谱确定了亚型特异性通路。

IF 5 2区医学

Neuropathology and Applied Neurobiology Pub Date : 2024-02-01 DOI: 10.1111/nan.12964

Abrar Younas, Neelam Younas, Muhammad Javed Iqbal, Isidre Ferrer, Inga Zerr

{"title":"Comparative interactome mapping of Tau-protein in classical and rapidly progressive Alzheimer's disease identifies subtype-specific pathways.","authors":"Abrar Younas, Neelam Younas, Muhammad Javed Iqbal, Isidre Ferrer, Inga Zerr","doi":"10.1111/nan.12964","DOIUrl":"10.1111/nan.12964","url":null,"abstract":"Aims: Tau is a key player in Alzheimer's disease (AD) and other Tauopathies. Tau pathology in the brain directly correlates with neurodegeneration in AD. The recent identification of a rapid variant of AD demands an urgent need to uncover underlying mechanisms leading to differential progression in AD. Accordingly, we aimed to dissect the underlying differential mechanisms of toxicity associated with the Tau protein in AD subtypes and to find out subtype-dependent biomarkers and therapeutic targets.Methods: To identify and characterise subtype-specific Tau-associated mechanisms of pathology, we performed comparative interactome mapping of Tau protein in classical AD (cAD) and rapidly progressive AD (rpAD) cases using co-immunoprecipitation coupled with quantitative mass spectrometry. The mass spectrometry data were extensively analysed using several bioinformatics approaches.Results: The comparative interactome mapping of Tau protein revealed distinct and unique interactors (DPYSL4, ARHGEF2, TUBA4A and UQCRC2) in subtypes of AD. Interestingly, an analysis of the Tau-interacting proteins indicated enrichment of mitochondrial organisation processes, including negative regulation of mitochondrion organisation, mitochondrial outer membrane permeabilisation involved in programmed cell death, regulation of autophagy of mitochondrion and necroptotic processes, specifically in the rpAD interactome. While, in cAD, the top enriched processes were related to oxidation-reduction process, transport and monocarboxylic acid metabolism.Conclusions: Overall, our results provide a comprehensive map of Tau-interacting protein networks in a subtype-dependent manner and shed light on differential functions/pathways in AD subtypes. This comprehensive map of the Tau-interactome has provided subsets of disease-related proteins that can serve as novel biomarkers/biomarker panels and new drug targets.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"50 1","pages":"e12964"},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

WNT-activated, MYC-amplified medulloblastoma displaying intratumoural heterogeneity. WNT激活、MYC扩增的髓母细胞瘤显示出瘤内异质性。

IF 5 2区医学

Neuropathology and Applied Neurobiology Pub Date : 2024-02-01 DOI: 10.1111/nan.12945

Sage Green, Travis Hoover, David Doss, Kimberly Davidow, Andrew W Walter, Catherine E Cottrell, Sidharth Mahapatra

引用次数: 0