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  1. Article: State-of-art modelling of inflammatory astrocyte-synapse interactions in injury and amyotrophic lateral sclerosis.

    Lakatos, András

    Neural regeneration research

    2017  Volume 12, Issue 1, Page(s) 75–76

    Language English
    Publishing date 2017-02-06
    Publishing country India
    Document type Journal Article
    ZDB-ID 2388460-5
    ISSN 1876-7958 ; 1673-5374
    ISSN (online) 1876-7958
    ISSN 1673-5374
    DOI 10.4103/1673-5374.198977
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Editorial: Primary Glial and Immune Cell Pathology in Neurodegenerative Diseases.

    Lakatos, András / Petzold, Gabor

    Frontiers in neurology

    2021  Volume 12, Page(s) 765376

    Language English
    Publishing date 2021-10-18
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2021.765376
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A human proteogenomic-cellular framework identifies KIF5A as a modulator of astrocyte process integrity with relevance to ALS.

    Szebényi, Kornélia / Barrio-Hernandez, Inigo / Gibbons, George M / Biasetti, Luca / Troakes, Claire / Beltrao, Pedro / Lakatos, András

    Communications biology

    2023  Volume 6, Issue 1, Page(s) 678

    Abstract: Genome-wide association studies identified several disease-causing mutations in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the contribution of genetic variants to pathway disturbances and their cell type-specific ... ...

    Abstract Genome-wide association studies identified several disease-causing mutations in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the contribution of genetic variants to pathway disturbances and their cell type-specific variations, especially in glia, is poorly understood. We integrated ALS GWAS-linked gene networks with human astrocyte-specific multi-omics datasets to elucidate pathognomonic signatures. It predicts that KIF5A, a motor protein kinesin-1 heavy-chain isoform, previously detected only in neurons, can also potentiate disease pathways in astrocytes. Using postmortem tissue and super-resolution structured illumination microscopy in cell-based perturbation platforms, we provide evidence that KIF5A is present in astrocyte processes and its deficiency disrupts structural integrity and mitochondrial transport. We show that this may underly cytoskeletal and trafficking changes in SOD1 ALS astrocytes characterised by low KIF5A levels, which can be rescued by c-Jun N-terminal Kinase-1 (JNK1), a kinesin transport regulator. Altogether, our pipeline reveals a mechanism controlling astrocyte process integrity, a pre-requisite for synapse maintenance and suggests a targetable loss-of-function in ALS.
    MeSH term(s) Humans ; Amyotrophic Lateral Sclerosis/genetics ; Astrocytes ; Genome-Wide Association Study ; Kinesins/genetics ; Proteogenomics
    Chemical Substances Kinesins (EC 3.6.4.4) ; KIF5A protein, human
    Language English
    Publishing date 2023-06-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-05041-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Conference proceedings: Special section on extended papers selected from the 2007 SID symposium (parts II-IV)

    Lakatos, Andras

    Special section on extended papers selected from the 2007 SID symposium (parts II-IV), [2007 SID international symposium was held in Long Beach, California, May 20 - 25], Jang, Jin. - San Jose, Cal. : Society for Information Display

    2008  

    Event/congress IDW (13, 2006.12.06-08, Otsu) ; International Display Workshops (13, 2006.12.06-08, Otsu)
    Document type Article ; Conference proceedings
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  5. Article ; Online: Cell-Free Mitochondrial DNA in Acute Brain Injury.

    Kayhanian, Saeed / Glynos, Angelos / Mair, Richard / Lakatos, Andras / Hutchinson, Peter J A / Helmy, Adel E / Chinnery, Patrick F

    Neurotrauma reports

    2022  Volume 3, Issue 1, Page(s) 415–420

    Abstract: Traumatic brain injury and aneurysmal subarachnoid haemorrhage are a major cause of morbidity and mortality worldwide. Treatment options remain limited and are hampered by our understanding of the cellular and molecular mechanisms, including the ... ...

    Abstract Traumatic brain injury and aneurysmal subarachnoid haemorrhage are a major cause of morbidity and mortality worldwide. Treatment options remain limited and are hampered by our understanding of the cellular and molecular mechanisms, including the inflammatory response observed in the brain. Mitochondrial DNA (mtDNA) has been shown to activate an innate inflammatory response by acting as a damage-associated molecular pattern (DAMP). Here, we show raised circulating cell-free (ccf) mtDNA levels in both cerebrospinal fluid (CSF) and serum within 48 h of brain injury. CSF ccf-mtDNA levels correlated with clinical severity and the interleukin-6 cytokine response. These findings support the use of ccf-mtDNA as a biomarker after acute brain injury linked to the inflammatory disease mechanism.
    Language English
    Publishing date 2022-09-28
    Publishing country United States
    Document type Journal Article
    ISSN 2689-288X
    ISSN (online) 2689-288X
    DOI 10.1089/neur.2022.0032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Human Stem Cell-Derived Astrocytes: Specification and Relevance for Neurological Disorders.

    Tyzack, Giulia / Lakatos, Andras / Patani, Rickie

    Current stem cell reports

    2016  Volume 2, Page(s) 236–247

    Abstract: Astrocytes abound in the human central nervous system (CNS) and play a multitude of indispensable roles in neuronal homeostasis and regulation of synaptic plasticity. While traditionally considered to be merely ancillary supportive cells, their complex ... ...

    Abstract Astrocytes abound in the human central nervous system (CNS) and play a multitude of indispensable roles in neuronal homeostasis and regulation of synaptic plasticity. While traditionally considered to be merely ancillary supportive cells, their complex yet fundamental relevance to brain physiology and pathology have only become apparent in recent times. Beyond their myriad canonical functions, previously unrecognised region-specific functional heterogeneity of astrocytes is emerging as an important attribute and challenges the traditional perspective of CNS-wide astrocyte homogeneity. Animal models have undeniably provided crucial insights into astrocyte biology, yet interspecies differences may limit the translational yield of such studies. Indeed, experimental systems aiming to understand the function of human astrocytes in health and disease have been hampered by accessibility to enriched cultures. Human induced pluripotent stem cells (hiPSCs) now offer an unparalleled model system to interrogate the role of astrocytes in neurodegenerative disorders. By virtue of their ability to convey mutations at pathophysiological levels in a human system, hiPSCs may serve as an ideal pre-clinical platform for both resolution of pathogenic mechanisms and drug discovery. Here, we review astrocyte specification from hiPSCs and discuss their role in modelling human neurological diseases.
    Language English
    Publishing date 2016-06-03
    Publishing country Switzerland
    Document type Review ; Journal Article
    ZDB-ID 2808623-5
    ISSN 2198-7866
    ISSN 2198-7866
    DOI 10.1007/s40778-016-0049-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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  7. Article: MEA-NAP compares microscale functional connectivity, topology, and network dynamics in organoid or monolayer neuronal cultures.

    Sit, Timothy Ph / Feord, Rachael C / Dunn, Alexander We / Chabros, Jeremi / Oluigbo, David / Smith, Hugo H / Burn, Lance / Chang, Elise / Boschi, Alessio / Yuan, Yin / Gibbons, George M / Khayat-Khoei, Mahsa / De Angelis, Francesco / Hemberg, Erik / Hemberg, Martin / Lancaster, Madeline A / Lakatos, Andras / Eglen, Stephen J / Paulsen, Ole /
    Mierau, Susanna B

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Microelectrode array (MEA) recordings are commonly used to compare firing and burst rates in neuronal cultures. MEA recordings can also reveal microscale functional connectivity, topology, and network dynamics-patterns seen in brain networks across ... ...

    Abstract Microelectrode array (MEA) recordings are commonly used to compare firing and burst rates in neuronal cultures. MEA recordings can also reveal microscale functional connectivity, topology, and network dynamics-patterns seen in brain networks across spatial scales. Network topology is frequently characterized in neuroimaging with graph theoretical metrics. However, few computational tools exist for analyzing microscale functional brain networks from MEA recordings. Here, we present a MATLAB MEA network analysis pipeline (MEA-NAP) for raw voltage time-series acquired from single- or multi-well MEAs. Applications to 3D human cerebral organoids or 2D human-derived or murine cultures reveal differences in network development, including topology, node cartography, and dimensionality. MEA-NAP incorporates multi-unit template-based spike detection, probabilistic thresholding for determining significant functional connections, and normalization techniques for comparing networks. MEA-NAP can identify network-level effects of pharmacologic perturbation and/or disease-causing mutations and, thus, can provide a translational platform for revealing mechanistic insights and screening new therapeutic approaches.
    Language English
    Publishing date 2024-04-11
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.05.578738
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Book: A Magyar esszé antológiája

    Domokos, Mátyás / Lakatos, András

    sorskérdések

    (Osiris klasszikusok)

    2006  

    Author's details válogatta és szerkesztette Domokos Mátyás
    Series title Osiris klasszikusok
    Keywords Hungary
    Language Hungarian
    Size v. <1-3>, 25 cm
    Publisher Osiris
    Publishing place Budapest
    Document type Book
    Note Vol. 3 edited by Mátyás Domokos and András Lakatos ; Vols. 2 and 3 include indexes
    ISBN 963389851X ; 9633898528 ; 9633898536 ; 9789633899250 ; 9789633898512 ; 9789633898529 ; 9789633898536 ; 9633899257
    Database Former special subject collection: coastal and deep sea fishing

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  9. Book: A Magyar esszé antológiája

    Domokos, Mátyás / Lakatos, András

    : sorskérdések

    (Osiris klasszikusok)

    2006  

    Author's details válogatta és szerkesztette Domokos Mátyás
    Series title Osiris klasszikusok
    Language Hungarian
    Size 25 cm
    Publisher Osiris
    Publishing place Budapest
    Document type Book
    ISBN 9633898528 ; 9789633898529
    Database Former special subject collection: coastal and deep sea fishing

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  10. Article ; Online: Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology.

    Szebényi, Kornélia / Wenger, Léa M D / Sun, Yu / Dunn, Alexander W E / Limegrover, Colleen A / Gibbons, George M / Conci, Elena / Paulsen, Ole / Mierau, Susanna B / Balmus, Gabriel / Lakatos, András

    Nature neuroscience

    2021  Volume 24, Issue 11, Page(s) 1542–1554

    Abstract: Amyotrophic lateral sclerosis overlapping with frontotemporal dementia (ALS/FTD) is a fatal and currently untreatable disease characterized by rapid cognitive decline and paralysis. Elucidating initial cellular pathologies is central to therapeutic ... ...

    Abstract Amyotrophic lateral sclerosis overlapping with frontotemporal dementia (ALS/FTD) is a fatal and currently untreatable disease characterized by rapid cognitive decline and paralysis. Elucidating initial cellular pathologies is central to therapeutic target development, but obtaining samples from presymptomatic patients is not feasible. Here, we report the development of a cerebral organoid slice model derived from human induced pluripotent stem cells (iPSCs) that recapitulates mature cortical architecture and displays early molecular pathology of C9ORF72 ALS/FTD. Using a combination of single-cell RNA sequencing and biological assays, we reveal distinct transcriptional, proteostasis and DNA repair disturbances in astroglia and neurons. We show that astroglia display increased levels of the autophagy signaling protein P62 and that deep layer neurons accumulate dipeptide repeat protein poly(GA), DNA damage and undergo nuclear pyknosis that could be pharmacologically rescued by GSK2606414. Thus, patient-specific iPSC-derived cortical organoid slice cultures are a reproducible translational platform to investigate preclinical ALS/FTD mechanisms as well as novel therapeutic approaches.
    MeSH term(s) Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; Astrocytes/metabolism ; Astrocytes/pathology ; C9orf72 Protein/genetics ; C9orf72 Protein/metabolism ; Frontotemporal Dementia/genetics ; Frontotemporal Dementia/metabolism ; Frontotemporal Dementia/pathology ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/pathology ; Neurons/metabolism ; Neurons/pathology ; Organ Culture Techniques/methods ; Organoids/metabolism ; Organoids/pathology
    Chemical Substances C9orf72 Protein ; C9orf72 protein, human
    Language English
    Publishing date 2021-10-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/s41593-021-00923-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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