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Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease

Translational Neurodegeneration 2021年第3期10卷 487-501页

作者： Neus Barranco Virginia Plá Daniel Alcolea Irene Sánchez‑Domínguez Reiner Fischer‑Colbrie isidro ferrer Alberto Lleó Fernando Aguado Department of Cell Biology Physiology and ImmunologyFaculty of BiologyUniversity of Barcelona08028 BarcelonaSpain Institute of Neurosciences University of Barcelona08028 BarcelonaSpain Memory Unit Department of NeurologySant Pau Biomedical Research Institute.Sant Pau HospitalAutonomous University of Barcelona08041 BarcelonaSpain Center for Net‑worked Biomedical Research on Neurodegenerative Diseases(CIBERNED) 28031 MadridSpain Department of Pharmacology Innsbruck Medical University6020 InnsbruckAustria Department of Pathology and Experi‑mental Therapeutics University of Barcelonaand Bellvitge University HospitalBellvitge Biomedical Research InstituteHospitalet de LlobregatSpain Pre‑sent Address:Center for Translational Neuromedicine University of Rochester Medical CenterRochesterNY 14642USA

Background:New fuid biomarkers for Alzheimer’s disease(AD)that reveal synaptic and neural network dysfunc‑tions are needed for clinical practice and therapeutic trial design.Dense core vesicle(DCV)cargos are promising cerebrospinal fuid(CSF)indicators of synaptic failure in AD patients.However,their value as biomarkers has not yet been determined.Methods:Immunoassays were performed to analyze the secretory proteins prohormone convertases PC1/3 and PC2,carboxypeptidase E(CPE),secretogranins SgIII and SgII,and Cystatin C in the cerebral cortex(n=45,provided by Bellvitge University Hospital)and CSF samples(n=66,provided by The Sant Pau Initiative on Neurodegeneration cohort)from AD patients(n=56)and age-matched controls(n=55).Results:In AD tissues,most DCV proteins were aberrantly accumulated in dystrophic neurites and activated astro‑cytes,whereas PC1/3,PC2 and CPE were also specifcally accumulated in hippocampal granulovacuolar degeneration bodies.AD individuals displayed an overall decline of secretory proteins in the CSF.Interestingly,in AD patients,the CSF levels of prohormone convertases strongly correlated inversely with those of neurodegeneration markers and directly with cognitive impairment status.Conclusions:These results demonstrate marked alterations of neuronal-specifc prohormone convertases in CSF and cortical tissues of AD patients.The neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD.

关键词： Alzheimer’s disease Biomarkers Cerebral cortex Cerebrospinal fuid Granulovacuolar degeneration PCSK1 PCSK2 Tau protein

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Ecto-GPR37:a potential biomarker for Parkinson’s disease

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Translational Neurodegeneration 2021年第1期10卷 77-90页

作者： Xavier Morato Paula Garcia-Esparcia Josep Argerich Franc Llorens Inga Zerr Wojciech Paslawski Eva Borras Eduard Sabido Ulla EPetaja-Repo Victor Fernandez-Duenas isidro ferrer Per Svenningsson Francisco Ciruela Pharm acology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaUHospitalet de LlobregatSpain Neuroscience Program Bellvitge Biomedical Research InstituteIDIBELLL'Hospitalet de LlobregatSpain Section of Neurology Department of Clinical NeuroscienceDepartm ent of NeuroscienceKarolinska InstituteStockholmSweden Neuropathology Unit Departm ent of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaL'Hospitalet de LlobregatSpain CIBERNED Centro de Investigacion Biomedica en Red de Enfermedades NeurodegenerativasInstituto CarlosⅢMadridSpain Department of Neurology Clinical Dementia Center and National Reference Center for CID SurveillanceUniversity Medical SchoolGottingenGermany German Center for Neurodegenerative Diseases GottingenGermany Proteomics Unit Center for Genomic RegulationBarcelonaSpain Proteomics Unit Universitat Pompeu FabraBarcelonaSpain Research Unit of Biomedicine Medical Research Center OuluUniversity of OuluOuluFinland

Objective:a-Synuclein has been studied as a potential biomarker for Parkinson's disease(PD)with no concluding results.Accordingly,there is an urgent need to find out reliable specific biomarkers for PD.GPR37 is an orphan G protein-coupled receptor that toxically accumulates in autosomal recessive juvenile parkinsonism.Here,we investigated whether GPR37 is upregulated in sporadic PD,and thus a suitable potential biomarker for PD.Methods:GPR37 protein density and mRNA expression in postmortem substantia nigra(SN)from PD patients were analysed by immunoblot and RT-qPCR,respectively.The presence of peptides from the N-terminus-cleaved domain of GPR37(i.***.ecto-GPR37)in human cerebrospinal fluid(CSF)was determined by liquid chromatography-mass spectrometric analysis.An engineered in-house nanoluciferase-based immunoassay was used to quantify ecto-GPR37 in CSF samples from neurological control(NC)subjects,PD patients and Alzheimer's disease(AD)patients.Results:GPR37 protein density and mRNA expression were significantly augmented in sporadic PD.Increased amounts of ecto-GPR37 peptides in the CSF samples from PD patients were identified by mass spectrometry and quantified by the in-house ELISA method.However,the CSF total a-synuclein level in PD patients did not differ from that in NC subjects.Similarly,the cortical GPR37 mRNA expression and CSF ecto-GPR37 levels in AD patients were also unaltered.Conclusion:GPR37 expression is increased in SN of sporadic PD patients.The ecto-GPR37 peptides are significantly increased in the CSF of PD patients,but not in AD patients.These results open perspectives and encourage further clinical studies to confirm the validity and utility of ecto-GPR37 as a potential PD biomarker.

关键词： GPR37 Pael-R Parkinson's disease Cerebrospinal fluid Biomarker Alzheimer's disease a-5ynuclein Orphan receptor

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嘿,我们是一组诗

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中华手工 2016年第5期 34-37页

作者：青桑 isidro ferrer

长了一双腿的鱼、只有四只脚的蚂蚁、没了尾巴的猴子……这是一个奇特的动物园。不仅如此,它们的面部表情被简略成加号、减号、除号,有些甚至只剩一个圆点。它们身体的形状更是千奇百怪,像漏斗、圆柱,甚至章鱼。当你迫不及待地想嘲笑它... 详细信息

长了一双腿的鱼、只有四只脚的蚂蚁、没了尾巴的猴子……这是一个奇特的动物园。不仅如此,它们的面部表情被简略成加号、减号、除号,有些甚至只剩一个圆点。它们身体的形状更是千奇百怪,像漏斗、圆柱,甚至章鱼。当你迫不及待地想嘲笑它们如此呆萌、奇特时,它们却能有力地回击你:嘿!我们是一组诗。

关键词：面部表情四只费雷尔你喜欢平面设计化妆舞会动物模型赤兔克托绝对自由

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奇异的编织装置——大象落地灯ELEPHANT

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国际纺织品流行趋势 2017年第1期 204-207页

作者： isidro ferrer 高红 Santiago Relanzón LZF Lab

坐标：西班牙La LZF Lamps,是西班牙一家专业生产薄木片灯具的公司,其作品是在意大利米兰国际灯展上展出的新的合作灯具系列。这一雕刻灯具系列来自于LZF Lamp公司isidro ferrer的合作,是艺术家和工匠展开跨领域的协作与突破创新的成果。

关键词： ELEPHANT 灯具设计意大利米兰动物造型奇异的薄木内衬

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Contralateral axillary metastasis:is surgical treatment the best option?

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Journal of Cancer Metastasis and Treatment 2019年第4期4卷 26-30页

作者： María Julia Giménez Jesús Manuel Patrón Giovanni Vento Ana Bayón Vincenzo Maisto isidro Bolumar Rosa ferrer Josep Asensi Joaquin Gavila Rafael Estevan Department of Surgery Fundación Instituto Valenciano de Oncología(IVO)Valencia 46007Espana

Contralateral axillary metastasis (CAM) is a rare entity normally treated as a systemic disease. Recent publications have proposed aggressive surgical treatment with benefits to the patients in terms of survival. We present a case of a 74-year-old patient with a history of unilateral breast cancer, recurrence on the ipsilateral breast and then development of a CAM. The patient was treated with aggressive surgical treatment, but she developed an early recurrence of the disease with distant metastasis. There is limited evidence of the correct management of CAM, although proposed to treat it as a loco regional disease, individualized and multidisciplinary management is the best option for these patients.

关键词： Breast cancer contralateral axillary metastasis lymphatic routes blockage

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