Excessive release of inorganic polyphosphate by ALS/FTD astrocytes causes non-cell-autonomous toxicity to motoneurons

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dc.contributor.authorArredondo, Cristian
dc.contributor.authorCefaliello, Carolina
dc.contributor.authorDyrda, Agnieszka
dc.contributor.authorJury, Nur
dc.contributor.authorMartinez, Pablo
dc.contributor.authorDíaz, Iván
dc.contributor.authorAmaro, Armando
dc.contributor.authorTran, Helene
dc.contributor.authorMorales, Danna
dc.contributor.authorPertusa, Maria
dc.contributor.authorStoica, Lorelei
dc.contributor.authorFritz, Elsa
dc.contributor.authorCorvalán, Daniela
dc.contributor.authorAbarzúa, Sebastián
dc.contributor.authorMéndez-Ruette, Maxs
dc.contributor.authorFernández, Paola
dc.contributor.authorRojas, Fabiola
dc.contributor.authorKumar, Meenakshi Sundaram
dc.contributor.authorAguilar, Rodrigo
dc.contributor.authorAlmeida, Sandra
dc.contributor.authorWeiss, Alexandra
dc.contributor.authorBustos, Fernando J.
dc.contributor.authorGonzález-Nilo, Fernando
dc.contributor.authorOtero, Carolina
dc.contributor.authorTevy, Maria Florencia
dc.contributor.authorBosco, Daryl A.
dc.contributor.authorSáez, Juan C.
dc.contributor.authorKähne, Thilo
dc.contributor.authorGao, Fen-Biao
dc.contributor.authorBerry, James D.
dc.contributor.authorNicholson, Katharine
dc.contributor.authorSena-Esteves, Miguel
dc.contributor.authorMadrid, Rodolfo
dc.contributor.authorVarela, Diego
dc.contributor.authorMontecino, Martin
dc.contributor.authorBrown, Robert H.
dc.contributor.authorvan Zundert, Brigitte
dc.date.accessioned2024-05-10T16:19:40Z
dc.date.available2024-05-10T16:19:40Z
dc.date.issued2022-05-18
dc.descriptionIndexación: Scopus.
dc.description.abstractNon-cell-autonomous mechanisms contribute to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), in which astrocytes release unidentified factors that are toxic to motoneurons (MNs). We report here that mouse and patient iPSC-derived astrocytes with diverse ALS/FTD-linked mutations (SOD1, TARDBP, and C9ORF72) display elevated levels of intracellular inorganic polyphosphate (polyP), a ubiquitous, negatively charged biopolymer. PolyP levels are also increased in astrocyte-conditioned media (ACM) from ALS/FTD astrocytes. ACM-mediated MN death is prevented by degrading or neutralizing polyP in ALS/FTD astrocytes or ACM. Studies further reveal that postmortem familial and sporadic ALS spinal cord sections display enriched polyP staining signals and that ALS cerebrospinal fluid (CSF) exhibits increased polyP concentrations. Our in vitro results establish excessive astrocyte-derived polyP as a critical factor in non-cell-autonomous MN degeneration and a potential therapeutic target for ALS/FTD. The CSF data indicate that polyP might serve as a new biomarker for ALS/FTD. © 2022 Elsevier Inc.
dc.description.urihttps://www-sciencedirect-com.recursosbiblioteca.unab.cl/science/article/pii/S0896627322001489?via%3Dihub
dc.identifier.citationNeuron, Volume 110, Issue 10, Pages 1656 - 1670.e12, 18 May 2022
dc.identifier.doi10.1016/j.neuron.2022.02.010
dc.identifier.issn0896-6273
dc.identifier.urihttps://repositorio.unab.cl/handle/ria/56676
dc.language.isoen
dc.publisherCell Press
dc.rights.licenseCC BY 4.0 DEED Atribución 4.0 Internacional
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectALS
dc.subjectAstrocytes
dc.subjectC9ORF72
dc.subjectCSF
dc.subjectFTD
dc.subjectiPSCs
dc.subjectMotor neurons
dc.subjectPolyP
dc.subjectSOD1
dc.subjectTARDBP
dc.titleExcessive release of inorganic polyphosphate by ALS/FTD astrocytes causes non-cell-autonomous toxicity to motoneurons
dc.typeArtículo
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