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Author Elena Galea

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Multi-Transcriptomic Analysis Points to Early Organelle Dysfunction in Human Astrocytes in Alzheimer’s Disease

Elena Galea, Laura Weinstock, Raquel Larramona-Arcas, Alyssa Pybus, Lydia Giménez-Llort, Carole Escartin, Levi Wood,

<h4>Background: </h4> Recent gene profiling of human AD astrocytes using single-nucleus RNA sequencing is limited by the low number of differentially expressed genes detected, and the small size of cohorts. We improved on prior studies with a novel systems-biology-based approach that can be used with available data from large cohorts.Methods ... Read more >>

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Multi-transcriptomic analysis points to early organelle dysfunction in human astrocytes in Alzheimer’s disease

Elena Galea, Laura Weinstock, Raquel Larramona-Arcas, Alyssa Pybus, Lydia Giménez-Llort, Carole Escartin, Levi Wood,

Recent single-nucleus RNA sequencing of astrocytes in postmortem Alzheimer’s disease (AD) samples is limited by the low number of sequenced astrocytes and small cohort sizes. We developed a systems biology approach to identify astrocytic genes in public large bulk AD transcriptomes. Brain cell specific gene clusters were generated from RNA ... Read more >>

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Reactive astrocyte nomenclature, definitions, and future directions.

Carole Escartin, Elena Galea, András Lakatos, James P O'Callaghan, Gabor C Petzold, Alberto Serrano-Pozo, Christian Steinhäuser, Andrea Volterra, Giorgio Carmignoto, Amit Agarwal, Nicola J Allen, Alfonso Araque, Luis Barbeito, Ari Barzilai, Dwight E Bergles, Gilles Bonvento, Arthur M Butt, Wei-Ting Chen, Martine Cohen-Salmon, Colm Cunningham, Benjamin Deneen, Bart De Strooper, Blanca Díaz-Castro, Cinthia Farina, Marc Freeman, Vittorio Gallo, James E Goldman, Steven A Goldman, Magdalena Götz, Antonia Gutiérrez, Philip G Haydon, Dieter H Heiland, Elly M Hol, Matthew G Holt, Masamitsu Iino, Ksenia V Kastanenka, Helmut Kettenmann, Baljit S Khakh, Schuichi Koizumi, C Justin Lee, Shane A Liddelow, Brian A MacVicar, Pierre Magistretti, Albee Messing, Anusha Mishra, Anna V Molofsky, Keith K Murai, Christopher M Norris, Seiji Okada, Stéphane H R Oliet, João F Oliveira, Aude Panatier, Vladimir Parpura, Marcela Pekna, Milos Pekny, Luc Pellerin, Gertrudis Perea, Beatriz G Pérez-Nievas, Frank W Pfrieger, Kira E Poskanzer, Francisco J Quintana, Richard M Ransohoff, Miriam Riquelme-Perez, Stefanie Robel, Christine R Rose, Jeffrey D Rothstein, Nathalie Rouach, David H Rowitch, Alexey Semyanov, Swetlana Sirko, Harald Sontheimer, Raymond A Swanson, Javier Vitorica, Ina-Beate Wanner, Levi B Wood, Jiaqian Wu, Binhai Zheng, Eduardo R Zimmer, Robert Zorec, Michael V Sofroniew, Alexei Verkhratsky,

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear ... Read more >>

Nat Neurosci (Nature neuroscience)
[2021, 24(3):312-325]

Cited: 67 times

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Amyloid-β impairs the phagocytosis of dystrophic synapses by astrocytes in Alzheimer's disease.

Maria V Sanchez-Mico, Sebastian Jimenez, Angela Gomez-Arboledas, Clara Muñoz-Castro, Carmen Romero-Molina, Victoria Navarro, Elisabeth Sanchez-Mejias, Cristina Nuñez-Diaz, Raquel Sanchez-Varo, Elena Galea, José C Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica,

Reactive astrocytes and dystrophic neurites, most aberrant presynaptic elements, are found surrounding amyloid-β plaques in Alzheimer's disease (AD). We have previously shown that reactive astrocytes enwrap, phagocytose, and degrade dystrophic synapses in the hippocampus of APP mice and AD patients, but affecting less than 7% of dystrophic neurites, suggesting reduced ... Read more >>

Glia (Glia)
[2021, 69(4):997-1011]

Cited: 2 times

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A roadmap to integrate astrocytes into Systems Neuroscience.

Ksenia V Kastanenka, Rubén Moreno-Bote, Maurizio De Pittà, Gertrudis Perea, Abel Eraso-Pichot, Roser Masgrau, Kira E Poskanzer, Elena Galea,

Systems neuroscience is still mainly a neuronal field, despite the plethora of evidence supporting the fact that astrocytes modulate local neural circuits, networks, and complex behaviors. In this article, we sought to identify which types of studies are necessary to establish whether astrocytes, beyond their well-documented homeostatic and metabolic functions, ... Read more >>

Glia (Glia)
[2020, 68(1):5-26]

Cited: 9 times

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Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence.

David Romeo-Guitart, Joaquim Forés, Mireia Herrando-Grabulosa, Raquel Valls, Tatiana Leiva-Rodríguez, Elena Galea, Francisco González-Pérez, Xavier Navarro, Valerie Petegnief, Assumpció Bosch, Mireia Coma, José Manuel Mas, Caty Casas,

Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):1879]

Cited: 24 times

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GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes.

Abel Eraso-Pichot, Marina Brasó-Vives, Arantxa Golbano, Carmen Menacho, Enrique Claro, Elena Galea, Roser Masgrau,

The prevalent view in neuroenergetics is that glucose is the main brain fuel, with neurons being mostly oxidative and astrocytes glycolytic. Evidence supporting that astrocyte mitochondria are functional has been overlooked. Here we sought to determine what is unique about astrocyte mitochondria by performing unbiased statistical comparisons of the mitochondriome ... Read more >>

Glia (Glia)
[2018, 66(8):1724-1735]

Cited: 10 times

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Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease.

Angela Gomez-Arboledas, Jose C Davila, Elisabeth Sanchez-Mejias, Victoria Navarro, Cristina Nuñez-Diaz, Raquel Sanchez-Varo, Maria Virtudes Sanchez-Mico, Laura Trujillo-Estrada, Juan Jose Fernandez-Valenzuela, Marisa Vizuete, Joan X Comella, Elena Galea, Javier Vitorica, Antonia Gutierrez,

Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components of intermediate filaments, is a common feature in brains of Alzheimer's patients. Reactive astrocytes are found in close association with neuritic plaques; however, the precise role of these glial cells in disease pathogenesis is unknown. In this ... Read more >>

Glia (Glia)
[2018, 66(3):637-653]

Cited: 49 times

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Author Correction: Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism.

Philip Hasel, Owen Dando, Zoeb Jiwaji, Paul Baxter, Alison C Todd, Samuel Heron, Nóra M Márkus, Jamie McQueen, David W Hampton, Megan Torvell, Sachin S Tiwari, Sean McKay, Abel Eraso-Pichot, Antonio Zorzano, Roser Masgrau, Elena Galea, Siddharthan Chandran, David J A Wyllie, T Ian Simpson, Giles E Hardingham,

This corrects the article DOI: 10.1038/ncomms15132. ... Read more >>

Nat Commun (Nature communications)
[2018, 9:16176]

Cited: 1 time

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CREB Regulates Distinct Adaptive Transcriptional Programs in Astrocytes and Neurons.

Luis Pardo, Luis Miguel Valor, Abel Eraso-Pichot, Angel Barco, Arantxa Golbano, Giles E Hardingham, Roser Masgrau, Elena Galea,

The cyclic AMP response element binding protein (CREB) is a primary hub of activity-driven genetic programs in neurons controlling plasticity, neurogenesis and survival. By contrast, the gene networks coordinated by CREB in astrocytes are unknown despite the fact that the astrocytic CREB is also activity-driven and neuroprotective. Herein we identified ... Read more >>

Sci Rep (Scientific reports)
[2017, 7(1):6390]

Cited: 6 times

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Should We Stop Saying 'Glia' and 'Neuroinflammation'?

Roser Masgrau, Carmen Guaza, Richard M Ransohoff, Elena Galea,

Central nervous system (CNS) therapeutics based on the theoretical framework of neuroinflammation have only barely succeeded. We argue that a problem may be the wrong use of the term 'neuroinflammation' as a distinct nosological entity when, based on recent evidence, it may not explain CNS disease pathology. Indeed, the terms ... Read more >>

Trends Mol Med (Trends in molecular medicine)
[2017, 23(6):486-500]

Cited: 32 times

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Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism.

Philip Hasel, Owen Dando, Zoeb Jiwaji, Paul Baxter, Alison C Todd, Samuel Heron, Nóra M Márkus, Jamie McQueen, David W Hampton, Megan Torvell, Sachin S Tiwari, Sean McKay, Abel Eraso-Pichot, Antonio Zorzano, Roser Masgrau, Elena Galea, Siddharthan Chandran, David J A Wyllie, T Ian Simpson, Giles E Hardingham,

The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, ... Read more >>

Nat Commun (Nature communications)
[2017, 8:15132]

Cited: 78 times

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Tauroursodeoxycholic bile acid arrests axonal degeneration by inhibiting the unfolded protein response in X-linked adrenoleukodystrophy.

Nathalie Launay, Montserrat Ruiz, Laia Grau, Francisco J Ortega, Ekaterina V Ilieva, Juan José Martínez, Elena Galea, Isidre Ferrer, Erwin Knecht, Aurora Pujol, Stéphane Fourcade,

The activation of the highly conserved unfolded protein response (UPR) is prominent in the pathogenesis of the most prevalent neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), which are classically characterized by an accumulation of aggregated or misfolded proteins. This activation is orchestrated ... Read more >>

Acta Neuropathol (Acta neuropathologica)
[2017, 133(2):283-301]

Cited: 18 times

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Targeted activation of CREB in reactive astrocytes is neuroprotective in focal acute cortical injury.

Luis Pardo, Agatha Schlüter, Luis M Valor, Angel Barco, Mercedes Giralt, Arantxa Golbano, Juan Hidalgo, Peilin Jia, Zhongming Zhao, Mariona Jové, Manuel Portero-Otin, Montserrat Ruiz, Lydia Giménez-Llort, Roser Masgrau, Aurora Pujol, Elena Galea,

The clinical challenge in acute injury as in traumatic brain injury (TBI) is to halt the delayed neuronal loss that occurs hours and days after the insult. Here we report that the activation of CREB-dependent transcription in reactive astrocytes prevents secondary injury in cerebral cortex after experimental TBI. The study ... Read more >>

Glia (Glia)
[2016, 64(5):853-874]

Cited: 16 times

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Cyclophilin D as a potential target for antioxidants in neurodegeneration: the X-ALD case.

Jone López-Erauskin, Isidre Ferrer, Elena Galea, Aurora Pujol,

X-linked adrenoleukodystrophy (X-ALD) is a severe inherited neurodegenerative disorder characterized by adrenal insufficiency and graded damage in the nervous system. Loss of function of the peroxisomal ABCD1 fatty-acid transporter, resulting in the accumulation of very long-chain fatty acids in organs and plasma, is the genetic cause. Treatment with a combination ... Read more >>

Biol Chem (Biological chemistry)
[2013, 394(5):621-629]

Cited: 4 times

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Pioglitazone halts axonal degeneration in a mouse model of X-linked adrenoleukodystrophy.

Laia Morató, Jorge Galino, Montserrat Ruiz, Noel Ylagan Calingasan, Anatoly A Starkov, Magali Dumont, Alba Naudí, Juan José Martínez, Patrick Aubourg, Manuel Portero-Otín, Reinald Pamplona, Elena Galea, M Flint Beal, Isidre Ferrer, Stéphane Fourcade, Aurora Pujol,

X-linked adrenoleukodystrophy is a neurometabolic disorder caused by inactivation of the peroxisomal ABCD1 transporter of very long-chain fatty acids. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative ... Read more >>

Brain (Brain : a journal of neurology)
[2013, 136(Pt 8):2432-2443]

Cited: 34 times

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JNK/ERK/FAK mediate promigratory actions of basic fibroblast growth factor in astrocytes via CCL2 and COX2.

Mathieu P Lichtenstein, José L M Madrigal, Aurora Pujol, Elena Galea,

While the role of cytokines in causing pro- and anti-inflammatory cascades in the brain and that of chemokines in promoting chemotaxis is well recognized, the immunomodulatory actions of neurotrophins released during brain injury remains largely undetermined. This knowledge gap affects basic fibroblast growth factor (FGF2), which in the brain is ... Read more >>

Neurosignals (Neuro-Signals)
[2012, 20(2):86-102]

Cited: 7 times

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Functional genomic analysis unravels a metabolic-inflammatory interplay in adrenoleukodystrophy.

Agatha Schlüter, Lluís Espinosa, Stéphane Fourcade, Jorge Galino, Eva López, Ekaterina Ilieva, Laia Morató, Muriel Asheuer, Ted Cook, Alistair McLaren, Juliet Reid, Fiona Kelly, Stewart Bates, Patrick Aubourg, Elena Galea, Aurora Pujol,

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) and (iii) a childhood variant, cALD, characterized by severe ... Read more >>

Hum Mol Genet (Human molecular genetics)
[2012, 21(5):1062-1077]

Cited: 36 times

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ATP and noradrenaline activate CREB in astrocytes via noncanonical Ca(2+) and cyclic AMP independent pathways.

Paulina Carriba, Luis Pardo, Arnaldo Parra-Damas, Mathieu P Lichtenstein, Carlos A Saura, Aurora Pujol, Roser Masgrau, Elena Galea,

In neurons, it is well established that CREB contributes to learning and memory by orchestrating the translation of experience into the activity-dependent (i.e., driven by neurotransmitters) transcription of plasticity-related genes. The activity-dependent CREB-triggered transcription requires the concerted action of cyclic AMP/protein kinase A and Ca(2+) /calcineurin via the CREB-regulated transcription ... Read more >>

Glia (Glia)
[2012, 60(9):1330-1344]

Cited: 8 times

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Staging anti-inflammatory therapy in Alzheimer's disease.

Mathieu P Lichtenstein, Paulina Carriba, Roser Masgrau, Aurora Pujol, Elena Galea,

The use of non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD) is controversial because conclusions from numerous epidemiological studies reporting delayed onset of AD in NSAID users have not been corroborated in clinical trials. The purpose of this personal view is to revise the case for NSAIDs in AD therapeutics ... Read more >>

Front Aging Neurosci (Frontiers in aging neuroscience)
[2010, 2:142]

Cited: 11 times

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Oxidative stress underlying axonal degeneration in adrenoleukodystrophy: a paradigm for multifactorial neurodegenerative diseases?

Elena Galea, Nathalie Launay, Manuel Portero-Otin, Montserrat Ruiz, Reinald Pamplona, Patrick Aubourg, Isidre Ferrer, Aurora Pujol,

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disorder expressed as four disease variants characterized by adrenal insufficiency and graded damage in the nervous system. X-ALD is caused by a loss of function of the peroxisomal ABCD1 fatty-acid transporter, resulting in the accumulation of very long chain fatty acids (VLCFA) in ... Read more >>

Biochim Biophys Acta (Biochimica et biophysica acta)
[2012, 1822(9):1475-1488]

Cited: 50 times

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Increasing CNS noradrenaline reduces EAE severity.

Maria Vittoria Simonini, Paul E Polak, Anthony Sharp, Susan McGuire, Elena Galea, Douglas L Feinstein,

The endogenous neurotransmitter noradrenaline (NA) is known to exert potent anti-inflammatory effects in glial cells, as well as provide neuroprotection against excitatory and inflammatory stimuli. These properties raise the possibility that increasing levels of NA in the central nervous system (CNS) could provide benefit in neurological diseases and conditions containing ... Read more >>

J Neuroimmune Pharmacol (Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology)
[2010, 5(2):252-259]

Cited: 35 times

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Secretase-independent and RhoGTPase/PAK/ERK-dependent regulation of cytoskeleton dynamics in astrocytes by NSAIDs and derivatives.

Mathieu P Lichtenstein, Paulina Carriba, María Antonia Baltrons, Beata Wojciak-Stothard, Jeffrey R Peterson, Agustina García, Elena Galea,

Profens like ibuprofen, R-flurbiprofen, or CHF5074 are being considered for the treatment of Alzheimer's disease because epidemiological data indicates that non-steroidal anti-inflammatory drugs are protective against neurodegeneration. Rho-GTPases are small G proteins, including RhoA, Cdc42, and Rac1, which control cytoskeleton dynamics. Because ibuprofen promotes axon growth via RhoA in neurons, ... Read more >>

J Alzheimers Dis (Journal of Alzheimer's disease : JAD)
[2010, 22(4):1135-1155]

Cited: 17 times

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Altered distribution of RhoA in Alzheimer's disease and AbetaPP overexpressing mice.

Gema Huesa, María Antonia Baltrons, Pilar Gómez-Ramos, Asunción Morán, Agustina García, Juan Hidalgo, Silvia Francés, Gabriel Santpere, Isidre Ferrer, Elena Galea,

RhoGTPases control cytoskeleton dynamics thereby modulating synaptic plasticity. Because Alzheimer's disease (AD) is characterized by synaptic dysfunction, we sought to determine whether the expression, activity, or localization of the GTPases RhoA, Rac1 and Cdc42, as well as p21-PAK, a downstream target of Rac1/Cdc42, were altered in 18-month-old AbetaPP Tg2576 mice ... Read more >>

J Alzheimers Dis (Journal of Alzheimer's disease : JAD)
[2010, 19(1):37-56]

Cited: 40 times

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Degeneration of noradrenergic fibres from the locus coeruleus causes tight-junction disorganisation in the rat brain.

Sergey Kalinin, Douglas L Feinstein, Hao-Liang Xu, Gema Huesa, Dale A Pelligrino, Elena Galea,

Although functional studies demonstrate that noradrenaline controls the permeability of the blood-brain barrier, it has never been determined whether this neurotransmitter regulates the tight junction (TJ) assembly that confers the barrier property to brain microvessels. We thus tested in rats the effect of pharmacological depletion of noradrenaline with the noradrenergic ... Read more >>

Eur J Neurosci (The European journal of neuroscience)
[2006, 24(12):3393-3400]

Cited: 32 times

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